Heteroatom containing cyclic dimers

ABSTRACT

The present invention provides cyclic dimers of alpha acids and polymers derived therefrom. Also provided are processes for preparing and methods of using the cyclic dimers and the polymers derived from the cyclic dimers.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority of U.S. provisional application No.61/596,843, filed Feb. 9, 2012, and U.S. provisional application No.61/597,444, filed Feb. 10, 2012, each of which is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

The invention relates to cyclic dimers of alpha acids and polymersderived therefrom, processes for preparing and methods of using cyclicdimers and polymers derived therefrom.

BACKGROUND OF THE INVENTION

Alpha acids are important molecules for a variety of purposes includingas industrial chemicals, feed additives, therapeutics, and various otheruses. Alpha acids include, for example, amino acids and alpha hydroxyacids. When two alpha acids react, they can form linear or cyclicdimers. When alpha acids react to form cyclic dimers the acid moiety isno longer free, and thus the cyclic dimers can have different physicalproperties such as reactivity, stability, and solubility, that can beadvantageous for certain applications.

For example, cyclic dimers can be used as compounds capable of releasingalpha acids. Cyclic dimers of alpha acids also may provide importantroutes for synthesizing polymers and copolymers of alpha acids. Forexample, lactic acid cyclic dimers, also called lactides, provide animportant route to polylactic acid, an important polymer which hasattracted significant interest due to its properties of beingbiocompatible and biodegradable, and for its suitability for uses in thebiomedical and industrial fields. Formation of lactide from lactic acidis complicated by competing oligomerization reactions. Most processesdeveloped for producing lactide compounds involved treatment at hightemperatures under a vacuum. For example, U.S. Pat. No. 5,274,073describes production of lactide by evaporating water from lactic acid togive an oligomer, and then mixing the oligomer with a depolymerizationcatalyst followed by thermal cracking to produce the lactide as a vapor.

Unlike lactide, cyclic dimers of alpha acids with heteroatom side chainmoieties have not been synthesized using the thermal cracking process.Heteroatom substituted cyclic dimers are desirable compounds becausethey can provide important functionalities for the numerous applicationsof the cyclic compounds. For example, substituted cyclic dimers mayprovide routes to functionalized and structurally diverse (i.e.branched, star, block) polymers and copolymers, which may have differentor enhanced properties over polylactic acid. Other methods forsynthesizing cyclic dimers have also failed for heteroatom containingalpha acids. A theoretical route to forming the cyclic compounds fromreaction of the halogen substituted monomers give poor yields becausethe halogenated monomer is unstable. Thus, routes to functionalizedcyclic dimers of alpha acids remain a synthetic challenge.

Thus, there is a need for heteroatom containing cyclic dimers as well asprocesses for making them.

SUMMARY OF THE INVENTION

The present invention relates to cyclic dimers of alpha acids, polymersprepared from cyclic dimers of alpha acids, methods for preparing cyclicdimers and polymers prepared therefrom, and uses of the cyclic dimersand polymers.

A first aspect of the invention encompasses a compound comprisingFormula (I):

wherein,

-   -   X¹ and X² are chosen from nitrogen and oxygen, provided that        both X¹ and X² are not nitrogen;    -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1;    -   provided that when Z is sulfur and n is 1, then R¹ and R³ are        other than hydrogen; and when Z is nitrogen, n is from 2 to 4,        and R³ is hydrogen, then R¹ is other than hydrogen or methyl.

Another aspect of the present disclosure provides a process forpreparing a compound comprising Formula (IX). The process comprises (a)contacting a compound comprising Formula (VI) with a compound comprisingFormula (VII) or a compound comprising Formula (VIII) and an acidcatalyst and (b) dehydrating the resulting reaction mixture to form thecompound comprising Formula (IX), the compounds comprising Formula (IX),(VI), (VII), and (VIII):

wherein,

-   -   X¹ is chosen from oxygen and nitrogen,    -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1.

A further aspect of the disclosure encompasses another method forpreparing a compound comprising Formula (IX). The process comprises (a)heating a compound comprising Formula (VI) with a compound comprisingFormula (VII) or a compound comprising Formula (VIII) to form a polymerand (b) heating the polymer at a temperature of about 200° C. and apressure of less than about 1 Torr to form the compound comprisingFormula (IX), the compounds comprising Formula (IX), (VI), (VII), and(VIII):

wherein,

-   -   X¹ is chosen from oxygen and nitrogen,    -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1.

Yet another aspect provides a polymer comprising a repeat unitcomprising Formula (XX):

wherein:

-   -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1.

Still another aspect of the present disclosure provides a polymercomprising Formula (XXI):

wherein:

-   -   R is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   X is chosen from oxygen and nitrogen; and    -   p is an integer greater than 1.

An additional aspect of the disclosure encompasses a process for forminga polymer. The process comprises contacting a plurality of compoundscomprising Formula (II):

-   -   with a catalyst to form the polymer comprising a repeat unit        comprising Formula (XX):

wherein:

-   -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and n is an integer ≧1.

Other features and iterations of the invention are described in moredetail herein.

REFERENCE TO COLOR FIGURES

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows the products formed after reaction of2-hydroxy-4-(methylthio)-butanoic acid (HMTBA) with hydrochloric acid.(A) shows an HPLC chromatogram in which the different products areidentified. (B) shows the same chromatogram as in (A) that is overlayedwith a chromatogram showing the elution profile of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione.

FIG. 2 shows the products formed after azeotropic distillation of2-hydroxy-4-(methylthio)-butanoic acid (HMTBA). (A) shows an HPLCchromatogram in which the different compounds are identified. (B) showsthe same chromatogram as in (A) that is overlayed with a chromatogramshowing the elution profile of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione.

FIG. 3 presents an ¹H NMR spectrum demonstrating the structure of thepolymer prepared from 3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione.

FIG. 4 shows gel permeation chromatograph traces monitoring ring openingpolymerization of 3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione as afunction of time.

FIG. 5 presents an HPLC chromatogram of the reaction mixture of ringopening polymerization of 3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5dione at 24 hours.

FIG. 6 shows HPLC analysis of the reaction mixture of the product shownin FIG. 5 after 2 hours of distillation at 200° C., 500 mTorr.

FIG. 7 presents HPLC analysis of distillates of the depolymerizationreaction after 2 hours of distillation at 200° C., 500 mTorr.

FIG. 8 presents an HPLC chromatogram of distillates of thedepolymerization reaction of polymer formed from HMTBa.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides cyclic dimers of alpha acids that may beused for many purposes. The invention also provides methods for makingthe cyclic dimers, compositions comprising the cyclic dimers, andmethods of using the cyclic dimers. Also provided are polymers preparedfrom the cyclic dimers, methods for preparing the polymers, andcompositions comprising the polymers. Advantageously, polymers of veryhigh molecular weight can be prepared from the cyclic dimers. The cyclicdimers and the polymers prepared from these cyclic dimers may be used,for example, as plasticizers, additives, processing aids, nutritiveagents, antioxidant agents, antimicrobial agents, and feed additives.

The cyclic dimers of alpha acids, as disclosed herein, have the generalstructure shown below. For purposes of discussion, the ring atoms arenumbered 1 to 6. Substitutions at the 3- and the 6-position may bedescribed as pendant groups to the cyclic structure. Where nostereochemistry is shown, it is intended to represent anystereochemistry.

(I) Cyclic Dimer Compounds

One aspect of the invention provides cyclic dimer compounds comprisingFormula (I):

wherein,

-   -   X¹ and X² are independently chosen from nitrogen and oxygen,        provided that both X¹ and X² are other than nitrogen;    -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1;    -   provided that when Z is sulfur and n is 1, then R¹ and R³ are        other than hydrogen; and when Z is nitrogen, n is from 2 to 4,        and R³ is hydrogen, then R¹ is other than hydrogen or methyl.

The heteroatoms, X¹ and X², at the 1- and 4-positions of the ring areindependently chosen from nitrogen and oxygen, provided that both arenot nitrogen. In some embodiments, the heteroatoms are in their neutralstate. Thus, where X¹ or X² is nitrogen, the nitrogen atom may befurther substituted with another substituent. Additional substitutionsof the heteroatom are preferably hydrogen, but may be chosen fromvarious other groups known in the art. In other embodiments, theheteroatoms may hold a charge. In some embodiments, X¹ and X² are bothoxygen. In other embodiments, X¹ is nitrogen and X² is oxygen. In stillanother embodiment, X¹ is oxygen and X² is nitrogen.

Each of R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ may be chosen from hydrogen,hydrocarbyl, or substituted hydrocarbyl. In various embodiments, thehydrocarbyl may be, but is not limited to, alkyl, cycloalkyl, alkenyl,alkenoxy, aryl, or alkylaryl. Substituted hydrocarbyl may be, withoutlimit, arylalkoxyl, alkoxy, alkoxycarbonyl, carbonyl, acyl, acyloxy,sulfonyl, sulfonyl halide, sulfonyl ester, carboxyl, carboxylic acid,hydroxyalkyl, alkyl halide, alkyl amine, alkyl amide, substituted alkylamine, or alkyl amide. In certain embodiments, R¹, R², R³, R⁴, R⁵, R⁶,and R⁷ may be chosen from hydrogen, alkyl, aryl, alkylaryl, substitutedalkyl, substituted aryl, and substituted alkylaryl. In various aspects,one or more of R², R³, R⁴, R⁵, R⁶, and R⁷ may be hydrogen. In anexemplary embodiment, each of R², R³, R⁴, and R⁵ is hydrogen.

In some embodiments, R² and R³ are independently chosen fromhydrocarbyl, substituted hydrocarbyl, and hydrogen. In some embodiments,R² and R³ are lower chain alkyl groups including methyl, ethyl, propyl,butyl, pentyl, and hexyl. In another embodiment R² and R³ are phenyl,benzyl, or substituted phenyl or benzyl. In preferred embodiments, R² ishydrogen and R³ is chosen from hydrogen, methyl, ethyl, phenyl, andbenzyl. In one embodiment, R² and R³ are hydrogen.

R⁴ and R⁵ are independently chosen from hydrogen, hydrocarbyl, andsubstituted hydrocarbyl. In some embodiments, (CR⁴R⁵)_(n) constitutes ahydrocarbyl chain, which may be linear or branched, with n representingthe number of linked carbon atoms in the chain. In various embodiments,n is equal to or greater than 1. In some embodiments, n ranges from 1 to20 and the hydrocarbyl chain comprises from 1 to 20 linked carbon atoms.In still another embodiment, n is equal to 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In exemplary embodiments, nis 1 or 2. In some embodiments, R⁴ and R⁵ may be hydrogen throughout thechain, in other aspects R⁴ and R⁵ are hydrocarbyl or substitutedhydrocarbyl throughout the chain.

R⁶ may be chosen from hydrogen, hydrocarbyl, substituted hydrocarbyl.Where R⁶ is a hydrocarbyl, it may be any alkyl chain but is preferably alower chain alkyl group such as methyl, ethyl, propyl, butyl, pentyl, orhexyl. The lower alkyl groups may additionally be branched or cyclic.Non-limiting examples include isopropyl, isobutyl, sec-butyl, t-butyl,cyclopropyl, cyclobutyl, cyclopentyl, and the like. In anotherembodiment, R⁶ is phenyl, benzyl, or substituted phenyl or benzyl. In anexemplary embodiment, R⁶ is methyl.

R⁷ may be optionally present in the compound comprising Formula (I).When present, R⁷ is chosen from hydrocarbyl, substituted hydrocarbyl,and hydrogen. Where R⁷ is a hydrocarbyl, it may be any alkyl group butis preferably a lower chain alkyl group such as methyl, ethyl, propyl,butyl, pentyl, or hexyl. The lower alkyl groups may additionally bebranched or cyclic, non-limiting examples include isopropyl, isobutyl,sec-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, and the like.In another embodiment, R⁷ may be phenyl, benzyl, or substituted phenylor benzyl. In a further embodiment, R⁷ may be hydrogen.

The compounds comprising Formula (I) also contain a heteroatom (Z). Insome embodiments, Z is nitrogen, selenium, or sulfur atom, includingsulfoxide and sulfone groups. The nitrogen, selenium, or sulfur atomsmay be charged and/or be present in various oxidation states within themolecule. Where the Z carries a charge, the compound may furthercomprise a counterion including, but not limited to lithium, sodium,potassium, calcium, magnesium, and the like.

In certain embodiments, when Z is sulfur and n is 1, then R¹ and R³ areother than hydrogen. In other embodiments, when Z is nitrogen, n is from2 to 4, and R³ is hydrogen, then R¹ is other than hydrogen or methyl.

In some embodiments, R¹ comprises (CR⁸R⁹)_(m)YR¹⁰R¹¹ and the compoundcomprises Formula (Ia):

wherein:

-   -   R², R³, R⁴, R⁵, R⁶, R⁷, X¹, X², Z, and n are as described above        for the compound comprising Formula (I);    -   R⁸, R⁹, and R¹⁰ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R¹¹ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Y is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   m is an integer ≧1.

Each of R⁸, R⁹, R¹⁰, and R¹¹ may be chosen from hydrogen, hydrocarbyl,and substituted hydrocarbyl. The hydrocarbyl may be, without limit,alkyl, cycloalkyl, alkenyl, alkenoxy, aryl, or alkylaryl. Thesubstituted hydrocarbyl may be, without limit, arylalkoxyl, alkoxy,alkoxycarbonyl, carbonyl, acyl, acyloxy, sulfonyl, sulfonyl halide,sulfonyl ester, carboxyl, carboxylic acid, hydroxyalkyl, alkyl halide,alkyl amine, alkyl amide, substituted alkyl amine, or alkyl amide. Incertain embodiments, each of R⁸, R⁹, R¹⁰, and R¹¹ may be chosen fromhydrogen, alkyl, aryl, alkylaryl, substituted alkyl, substituted aryl,and substituted alkylaryl. In various aspects, one or more of R⁸, R⁹,R¹⁰, and R¹¹ may be hydrogen. In an exemplary embodiment, R³, R⁸, and R⁹are hydrogen.

Where R¹⁰ is a hydrocarbyl, it may be any alkyl chain but is preferablya lower chain alkyl group such as methyl, ethyl, propyl, butyl, pentyl,or hexyl. The lower alkyl groups may additionally be branched or cyclic.Non-limiting examples include isopropyl, isobutyl, sec-butyl, t-butyl,cyclopropyl, cyclobutyl, cyclopentyl, and the like. In anotherembodiment, R¹⁰ is phenyl, benzyl, or substituted phenyl or benzyl. Inan exemplary embodiment, R¹⁰ is methyl.

R¹¹ may be optionally present in the compound comprising Formula (Ia).When present, R¹¹ is chosen from hydrocarbyl, substituted hydrocarbyl,and hydrogen. Where R¹¹ is hydrocarbyl, it may be any alkyl group but ispreferably a lower chain alkyl group such as methyl, ethyl, propyl,butyl, pentyl, or hexyl. The lower alkyl groups may additionally bebranched or cyclic, non-limiting examples include isopropyl, isobutyl,sec-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, and the like.In another embodiment, R¹¹ may be phenyl, benzyl, or substituted phenylor benzyl. In a further embodiment, R¹¹ may be hydrogen.

In some embodiments, (CR⁸R⁹)_(m) constitutes a hydrocarbyl chain, whichmay be linear or branched, with m representing the number of linkedcarbon atoms in the chain. In various embodiments, m is equal to orgreater than 1. In some embodiments, m ranges from 1 to 20 and thehydrocarbyl chain comprises from 1 to 20 linked carbon atoms. In stillanother embodiment, m is equal to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, or 20. In exemplary embodiments, m is 1 or2. In some embodiments, R⁸ and R⁹ may be hydrogen throughout the chain,in other aspects R⁸ and R⁹ are hydrocarbyl or substituted hydrocarbylthroughout the chain.

The compounds comprising Formula (Ia) also contain a heteroatom (Y). Insome embodiments, Y is nitrogen, selenium, or sulfur atom, includingsulfoxide and sulfone groups. The nitrogen, selenium, or sulfur atomsmay be charged and/or be present in various oxidation states within themolecule. Where the Y carries a charge, the compound may furthercomprise a counterion including, but not limited to lithium, sodium,potassium, calcium, magnesium, and the like.

In one embodiment, R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen, n and mindependently range from 1 to 10; Z and Y are independently chosen fromsulfur, sulfone, sulfoxide, and selenium. In some iterations, R⁶ and R¹⁰are lower chain alkyl, and R⁷ and R¹¹, if present, are independentlyhydrogen or lower chain alkyl.

Non-limiting compounds comprising Formula (I) or Formula (Ia) are listedin Table 1.

TABLE 1 Exemplary compounds comprising Formulas (I) or (IIa). # X¹ X² Zn R¹ R³ R⁴ R⁵ R⁶ R⁷ 1 N O S 1 (CH₂)₂SCH₃ H H H CH₃ — 2 N O S 1 CH₂SCH3 HH H CH₂CH₃ — 3 N O S 2 CH₃ H H H CH₃ CH₃ 4 N O S 2 CH₂Ph H H H CH₂CH₃CH₃ 5 N O SO 1 CH₃ H H H CH₃ — 6 N O SO 1 (CH₂)₂SCH₃ H H H CH₃ — 7 N OSO 2 (CH₂)₂SOCH₃ H H H CH₃ — 8 N O SO 2 (CH₂)₂SeCH₃ H H H CH₂CH₃ — 9 N OSO₂ 1 CH₂Ph H H H CH₂CH₃ — 10 N O SO₂ 1 CH₃ H H H CH₃ — 11 N O SO₂ 2(CH₂)₂SCH₃ H H H Ph — 12 N O SO₂ 2 (CH₂)₂SOCH₃ H H H CH₂CH₃ — 13 N O SO₂2 (CH₂)₂SOCH₃ H H H CH₃ 14 N O SO₂ 2 (CH₂)₂SO₂CH₃ H H H CH₃ — 15 N O SO2 (CH₂)₂SO₂CH₃ H H H CH₃ — 16 N O N 1 (CH₂)₂N(CH₃)CH₂ H H H CH₂CH₃ CH₃CH₃ 17 N O Se 1 CH₂SeCH₃ H H H CH₃ — 18 N O Se 2 (CH₂)₂SeCH₃ H H H CH₃ —19 O N S 1 (CH₂)₂SCH₃ H H H CH₃ — 20 O N S 1 CH₂SCH3 H H H CH₂CH₃ — 21 ON S 2 CH₃ H H H CH₃ CH₃ 22 O N S 2 CH₂Ph H H H CH₂CH₃ CH₃ 23 O N SO 1CH₃ H H H CH₃ — 24 O N SO 1 (CH₂)₂SCH₃ H H H CH₃ — 25 O N SO 2(CH₂)₂SO₂CH₃ H H H CH₃ — 26 O N SO 2 (CH₂)₂SeCH₃ H H H CH₂CH₃ — 27 O NSO₂ 1 CH₂Ph H H H CH₂CH₃ — 28 O N SO₂ 1 CH₃ H H H CH₃ — 29 O N SO₂ 2(CH₂)₂SCH₃ H H H CH₃ — 30 O N SO₂ 2 (CH₂)₂SOCH₃ H H H CH₂CH₃ — 31 O NSO₂ 2 (CH₂)₂SOCH₃ H H H CH₃ 32 O N SO₂ 2 (CH₂)₂SO₂CH₃ H H H CH₃ 33 O N N1 (CH₂)₂N(CH₃)CH₂ H H H CH₂CH₃ CH₃ CH₃ 34 O N Se 1 CH₂SeCH₃ H H H CH₃ —35 O N Se 2 (CH₂)₂SeCH₃ H H H CH₃ — 36 O O S 1 (CH₂)₂SCH₃ H H H Ph — 37O O S 1 CH₂SCH3 H H H CH₂CH₃ — 38 O O S 2 CH₃ H H H CH₃ CH₃ 39 O O S 2CH₂Ph H H H CH₂CH₃ CH₃ 40 O O SO 1 CH₃ H H H CH₃ — 41 O O SO 1(CH₂)₂SCH₃ H H H CH₃ — 42 O O SO 2 (CH₂)₂SO₂CH₃ H H H CH₃ 43 O O SO 2(CH₂)₂SOCH₃ H H H CH₃ — 44 O O SO 2 (CH₂)₂SeCH₃ H H H CH₂CH₃ — 45 O O SO2 (CH₂)₂SOCH₃ H H H CH₃ 46 O O SO₂ 1 CH₂Ph H H H CH₂CH₃ — 47 O O SO₂ 1CH₃ H H H CH₃ — 48 O O SO₂ 2 (CH₂)₂SCH₃ H H H CH₃ — 49 O O SO₂ 2(CH₂)₂SOCH₃ H H H CH₂CH₃ — 50 O O SO₂ 2 (CH₂)₂SO₂CH₃ H H H CH₃ 51 O O N1 (CH₂)₂NCH₃CH₂C H H H CH₂CH₃ CH₃ H₃ 52 O O Se 1 CH₂SeCH₃ H H H Ph — 53O O Se 2 (CH₂)₂SeCH₃ H H H CH₃ — 54

55

56

57

In an alternative embodiment, the compound comprises Formula (II):

wherein,

-   -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1;    -   provided that when Z is sulfur and n is 1, then R¹ and R³ are        other than hydrogen; and when Z is nitrogen, n is 2 or 4, and R³        is hydrogen, then R¹ is other than methyl.

Each of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n may be chosen as describedfor Formula (I). In some embodiments of the compound comprising Formula(II), when Z is nitrogen, then either both R¹ and R³ are methyl orneither R¹ nor R³ is methyl. In another embodiment in which Z is sulfur,then R⁶ is not hydrogen or benzyl. In yet another embodiment in which Zis sulfur and n is 1, then R⁶ is not hydrogen, benzyl, orparamethoxybenzyl.

In one embodiment, the compound comprises Formula (IIb):

wherein;

-   -   R¹ and R⁶ are independently chosen from hydrogen, alkyl, aryl,        alkylaryl, substituted alkyl, substituted aryl, and substituted        alkylaryl.

In some embodiments, R¹ is chosen from methyl, ethyl, phenyl, andbenzyl; and R⁶ is chosen from hydrogen, methyl, and ethyl. In anexemplary embodiment, both R¹ and R⁶ are methyl, as in the compoundcomprising Formula (IIc):

The atoms at the 3- and 6-positions of the ring of the compoundcomprising Formula (IIb) or Formula (IIc) may have a configurationchosen from RR, RS, SR, and SS, respectively.

In additional embodiments, R¹ of the compound comprising Formula (II)comprises (CR⁸R⁹)_(m)YR¹⁰R¹¹ such that the compound comprises Formula(IIa):

wherein:

-   -   R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n are as described above for the        compounds comprising Formula (II);    -   R⁸, R⁹, and R¹⁰ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R¹¹ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Y is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   m is an integer ≧1.

Each of R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n may be chosen as described forcompounds comprising Formula (I), and each of R⁸, R⁹, R¹⁰, R¹¹, Y and mmay be chosen as described for compounds comprising Formula (Ia).

In some embodiments of the compound comprising Formula (IIa), the twopendant groups do not comprise a lysine or lysine derivative. In someembodiments, when Z and Y are nitrogen, and n and m are 4 or 5, then R⁶and R¹⁰ are not hydrogen or COOR⁸, and R⁸ and R¹¹ are chosen fromhydrogen, benzyl, and t-butyl.

In various embodiments, R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen, n and mindependently range from 1 to 10; Z and Y are independently chosen fromsulfur, sulfone, sulfoxide, and selenium. In some iterations, R⁶ and R¹⁰are lower chain alkyl, and R⁷ and R¹¹, if present, are independentlyhydrogen or lower chain alkyl. In an exemplary embodiment, each of R²,R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen, both n and m are 2, both Z and Y aresulfur, both R⁶ and R¹⁰ are methyl, and neither R⁷ nor R¹¹ are present.

Non-limiting examples of compounds comprising Formula (II) or Formula(IIa) are shown in Table 2.

TABLE 2 Exemplary compounds comprising Formulas (II) or (IIa). 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

In still other embodiments, the compound comprises Formula (III):

wherein,

-   -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer to ≧1.

Each of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n may be chosen as describedfor Formula (I).

In some embodiments, R¹ of the compound comprising Formula (III)comprises (CR⁸R⁹)_(m)YR¹⁰R¹¹ and the compound comprises Formula (IIIa):

wherein:

-   -   R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n are as described above for the        compound comprising Formula (III);    -   R⁸, R⁹, and R¹⁰ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R¹¹ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Y is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   m is an integer ≧1.

Each of R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n may be chosen as described forcompounds comprising Formula (I), and each of R⁸, R⁹, R¹⁰, R¹¹, Y and mmay be chosen as described for compounds comprising Formula (Ia).

In various embodiments, R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen, n and mindependently range from 1 to 10; Z and Y are independently chosen fromsulfur, sulfone, sulfoxide, and selenium. In some iterations, R⁶ and R¹⁰are lower chain alkyl, and R⁷ and R¹¹, if present, are independentlyhydrogen or lower chain alkyl.

Non-limiting compounds comprising Formula (III) or Formula (IIIa) arepresented in Table 3.

TABLE 3 Exemplary compounds comprising Formulas (III) or (IIIa). 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

Yet another embodiment provides a compound comprising Formula (IV):

wherein,

-   -   R⁶ and R¹⁰ are independently chosen from hydrogen, hydrocarbyl,        and substituted hydrocarbyl;    -   R⁷ and R¹¹ are optionally present, when present each is        independently chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   Z and Y are independently chosen from sulfone, sulfoxide, and        selenium; and    -   n and m are integers ≧1;    -   provided that when Z and Y are sulfoxide, then R⁶ and R¹⁰ are        other than methyl.

Each of R⁶, R⁷, R¹⁰, R¹¹, Y, Z, n, and m may be chosen as describedabove for compounds comprising Formulas (I) and (Ia).

In one embodiment of the compound comprising Formula (IV), Y and Z areselenium, R⁶ and R¹⁰ are lower alkyl, and R⁷ and R¹¹ are not present. Inanother embodiment, Y and Z are selenium, R⁶ and R¹⁰ are methyl, and R⁷and R¹¹ are not present. Table 4 lists non-limiting examples ofcompounds comprising Formula (IV).

TABLE 4 Exemplary compounds comprising Formula (IV). 1

2

3

4

5

6

7

8

9

10

In exemplary embodiments, the compound of the invention comprisesFormula (V):

TABLE 5 Exemplary compounds comprising Formula (V). 1

2

3

4

In some aspects of the invention, the compounds comprise one or morechiral centers. Each chiral center of the compounds comprising Formulas(I), (II), (III), (IV), and (V) may have an R or an S configuration. Insome embodiments, where the carbon atom at the 3-position and the6-position has four different substituents, the positions are chiralcenters. In such embodiments, the configurations at the 3- and6-positions may be chosen from RR, RS, SR, and SS, respectively. Inanother aspect, compositions may be mixtures of two or more isomers. Inanother aspect, the compositions may be optically pure or enriched withone or more isomers. In aspects of the invention where the pendentgroups at the 3- and 6-positions are the same, the compounds maycomprise the D-isomer, the L-isomer, or the meso isomer. In anotherembodiment, the composition may be a mixture of two or more of theD-isomer, the L-isomer, and the meso isomer.

The compounds of the invention may also be provided as substantiallypure compounds. In some aspects, the compounds are substantially pure inmixtures of stereoisomers that are substantially free from byproductsincluding monomers, non-cyclic dimers, or other oligomers. In anotheraspect, the compounds described herein may be provided as asubstantially pure enantiomer or diastereomer. By substantially pure, itis meant that the desired compound is present in about 80% purity, about90% purity, or about 95% purity, about 99% purity, about 99.5% purity,about 99.9% purity, 99.99% purity, or higher. In another embodiment, thecompounds may be provided as optically pure compounds, optically purecompounds may have about 80%, about 90%, about 99% optical purity, about99.9%, or about 99.99% optical purity, or higher.

The compounds provided in this section may have a variety of uses andpurposes, in their cyclic forms or as polymers (see below). Thecompounds or compositions comprising the compounds provided herein mayhave one set of properties under one set of conditions and differentproperties under different conditions. In some embodiments, thecompounds provided herein may be stable in aqueous solutions underapproximately neutral pH. In other embodiments, the compounds providedherein may hydrolyze in aqueous solutions at pH values of less thanabout 6.0, less than about 5.0, less than about 3.0, less than about2.0, or less than about 1.0.

(II) Processes for Preparing Cyclic Dimers

Still another aspect of the present disclosure encompasses processes forthe preparation of the compounds disclosed herein. In particular,processes for the preparation of the cyclic dimers comprise contactingalpha acids under conditions such that the alpha acids form cyclicdimers.

(a) Preparation of Compounds Comprising Formula (IX)—Condensation

In one aspect, the process for producing a compound comprising Formula(IX) comprises (a) contacting a compound comprising Formula (VI) with acompound comprising Formula (VII) or a compound comprising Formula(VIII) and an acid catalyst and (b) dehydrating the resulting reactionmixture to form the compound comprising Formula (IX). The compoundscomprising Formula (IX), (VI), (VII), and (VIII) have the followingstructures:

wherein,

-   -   X¹ is chosen from oxygen and nitrogen,    -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1.

R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n may be chosen as described abovefor the compound comprising Formula (I) in section (I). In someembodiments, R¹ may be (CR⁸R⁹)_(m)YR¹⁰R¹¹, wherein R⁸, R⁹, R¹⁰, R¹¹, Yand m may be chosen as described for compounds comprising Formula (Ia)in section (I).

In some embodiments, the process proceeds according to Reaction Scheme1(a) to form the compound comprising Formula (II):

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n are as defined above.

In still other embodiments, the reaction proceeds according to ReactionScheme 1(b) to form the compound comprising Formula (III):

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n are as defined above.

The compound comprising Formula (VII) may be an amino acid. Non-limitingexamples of suitable amino acids include glycine, alanine, valine,leucine, isoleucine, phenylalanine, serine, threonine, lysine,Δ-hydroxylysine, ornithine, aspartic acid, glutamic acid, cysteine,cystine, methionine, selenomethionine, tyrosine, thyroxine, proline,hydroxyproline, and tryptophan. In some aspects, the amino acid does notrequire protection. In other aspects, the amino acid may be protected,for example on the side chain side chain or at the N-terminus by meansknown in the art.

The process comprises contacting the compound comprising Formula (VI)with a compound comprising Formula (VII) or a compound comprisingFormula (VIII). In general, the two compounds are provided to thereaction in an approximately equal molar ratio. In some embodiments, thecompound comprising Formula (VI) may be provided in a molar ratio withrespect to the compound comprising Formula (VII) or Formula (VIII) ofabout 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1; 0.7:1, 0.8:1, 0.9:1,1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:2.0,1:2.5, 1:3, or about 1:3.5. In a preferred embodiment, the compoundcomprising Formula (VI) is provided in a 1:1 molar ratio with thecompound comprising Formula (VII) or Formula (VIII).

In some aspects, the reaction may be conducted under dehydrationconditions in the presence of an acid catalyst. In some embodiments, thestarting materials are purified to a low water concentration prior tothe contacting step. For example, the starting materials comprising thecompounds of Formulas (VI) and (VII) or (VIII) may be provided to thereaction mixture with a water content below about 5%, below about 3%,below about 2%, or below about 1%.

A variety of acid catalysts may be suitable to produce the compoundcomprising Formula (IX). In some embodiments, the acid catalyst may bechosen from organic acids, inorganic acids, and solid resins. Exemplaryacid catalysts include, without limitation, phosphoric acid, aceticacid, boric acid, hydrochloric acid, trifluoroacetic acid,methanesulfonic acid, ortho- meta- and para-toluenesulfonic acid,polyphosphoric acid, sulfuric acid, tosylic acid, xylenesulfonic acid,Dowex resins, Amberlyst resins, Zn dust, and Sn based catalysts (suchas, for example, Sn dust, tin oxide, tin (II) chloride, dibutyltindilaurate, and stannous octoate), germanium dioxide, antimony trioxide,zinc oxide, iron (III) oxide, aluminum oxide, silicon dioxide, titaniumdioxide, mixtures and combinations thereof.

The acid catalyst may be added in a range of ratios to the compoundscomprising Formulas (VI) and (VII) or (VIII). In some aspects the amountof catalyst added may range from 0.0001 mol % of the amount of thecompounds comprising Formulas (VI) and (VII) or (VIII) to about 5 mol %of the compounds comprising Formulas (VI) and (VII) or (VIII). In someembodiments, the acid catalyst is added in an amount below 5 mol %,below 2 mol %, or below 1 mol %. More preferably, the acid catalyst isprovided in the reaction in a molar ratio of about 0.001, 0.002, 0.003,0.004, 0.005, 0.006, 0.007, 0.008, 0.009, or 0.010 mol % to the compoundcomprising Formula (VI).

The reaction may be conducted under dehydration conditions to promoteformation of the cyclic dimer. In certain embodiments, dehydration maybe accomplished via distillation. For example, the reaction may besubjected to simple distillation, fractional distillation, azeotropicdistillation, steam distillation, vacuum distillation, distillationusing a Dean Stark trap or another similar trap, azeotropic distillationusing a Dean Stark or another similar trap, and the like. In otherembodiments, dehydration may be accomplished via a drying reagent whichmay include molecular sieves, calcium sulfate, magnesium sulfate, sodiumsulfate, potassium hydroxide, potassium carbonate, and the like.

The temperature at which the reaction takes place may vary in differentembodiments and over the course of the reaction. In one embodiment, thereaction may be carried out at a temperature ranging from about 100° C.and about 200° C. In another embodiment, the reaction may be conductedat a temperature of about 100° C., 110° C., 120° C., 130° C., 140° C.,150° C., 160° C., 170° C., 180° C., 190° C., 200° C., or at a rangebetween and including any two of these values. In another embodiment,the temperature may range from about 130° C. and about 150° C. In yetanother embodiment, the temperature may range from about 110° C. andabout 120° C. In general, the reaction is conducted at atmosphericpressure, but in certain embodiments, the reaction may also be conductedabove or below atmospheric pressure.

The process may be performed in the presence of a solvent or thereaction may be performed neat. Where the reaction includes a solvent,the type of solvent may vary depending upon the identities of thereactants. Thus, the solvent may be a nonpolar solvent, a protic polarsolvent, an aprotic polar solvent, or a combination thereof.Non-limiting examples of suitable nonpolar solvents include anisole,benzene, butyl acetate, tert-butyl methyl ether, chlorobenzene,chloroform, chloromethane, cyclohexane, dichloromethane, dichloroethane,di-tert-butyl ether, dimethyl ether, diethylene glycol, diethyl ether,diglyme, diisopropyl ether, ethyl tert-butyl ether, ethylene oxide,fluorobenzene, heptane, hexane, methyl tert-butyl ether, toluene, xyleneand combinations thereof. Examples of suitable protic polar solventsinclude without limit water, alcohols (e.g., methanol, ethanol,isopropanol, n-propanol, isobutanol, n-butanol, s-butanol, t-butanol),diols (e.g., propylene glycol and the like), organic acids (e.g., formicacid, acetic acid, and so forth), amides (e.g., formamide, acetamide,and the like), and combinations of any of the above. Non-limitingexamples of suitable aprotic polar solvents include acetone,acetonitrile, diethoxymethane, N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), N,N-dimethylpropionamide,1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU),1,3-dimethyl-2-imidazolidinone (DMI), 1,2-dimethoxyethane (DME),dimethoxymethane, bis(2-methoxyethyl)ether, N,N-dimethylacetamide(DMAC), N-methyl-2-pyrrolidinone (NMP), 1,4-dioxane, ethyl acetate,ethyl formate, formamide, hexachloroacetone, hexamethylphosphoramide,methyl acetate, N-methylacetamide, methylethyl ketone, methylisobutylketone, N-methylformamide, methylene chloride, methoxyethane,morpholine, nitrobenzene, nitromethane, propionitrile, propyl acetates,sulfolane, tetramethylurea, tetrahydrofuran (THF), 2-methyltetrahydrofuran, tetrahydropyran, trichloromethane, and combinationsthereof. In exemplary embodiments, the solvent is chosen from toluene,xylene, anisole, and mixtures thereof.

The weight-to-weight ratio of the solvent to the compounds comprisingFormulas (VI) and (VII) or (VIII) can and will vary. Typically, theweight-to-weight ratio of the solvent to the compounds comprisingFormulas (VI) and (VII) or (VIII) may range from about 1:1 to about100:1. In various embodiments, the weight-to-weight ratio of the solventto the compounds comprising Formulas (VI) and (VII) or (VIII) may rangefrom about 1:1 to 5:1, from about 5:1 to about 20:1, from about 20:1 toabout 40:1, from about 40:1 to about 80:1, or from about 80:1 to about100:1. In some embodiments, the weight-to-weight ratio of the solvent tothe compounds comprising Formulas (VI) and (VII) or (VIII) may be about30:1, or about 60:1.

The duration of the reaction can and will vary. In general, the reactionmay be allowed to proceed from several hours to several days. Typically,however, the reaction is allowed to proceed for a sufficient period oftime until the reaction is complete, as determined by means well knownto those of skill in the art. In this context, the final reactionmixture contains a significantly diminished amount of the compoundscomprising Formulas (VI) and (VII) or (VIII) and a significantlyincreased amount of the compound comprising Formula (IX) compared to theamounts of each present at the beginning of the reaction. In someembodiments, the reaction may be allowed to proceed for a period of timeranging from about 1 hour to about 10 hours. In another embodiment, thereaction may be allowed to proceed for a period of time ranging fromabout 1 hour to about 5 hours. In a preferred embodiment, the reactionmay be allowed to proceed for a period for about 3 hours to about 5hours.

The yield of the compound comprising Formula (IX) can and will vary. Ingeneral, yield of the compound comprising Formula (IX) will be at leastabout 15%, at least about 20%, 30%, at least about 40%, at least about50%, at least about 60%, at least about 70%, at least about 80%, or atleast about 90%.

The compound comprising Formula (IX) may be isolated from the reactionmixture and/or purified by means including by size exclusionchromatography, high performance liquid chromatography (HPLC),ion-exchange chromatography, chiral chromatography, other types ofchromatography, precipitation, distillation, or crystallization.

(b) Preparation of Compounds Comprising Formula (IX)—Polymerization andThermal Cracking

In other embodiments, the compound comprising Formula (IX) may beprepared by (a) heating a compound comprising Formula (VI) with acompound comprising Formula (VII) or a compound comprising Formula(VIII) such that a polymer is formed and then (b) heating the polymer atan increased temperature and reduced pressure to form the cyclic dimercompound comprising Formula (IX). The reactants, i.e., the compoundscomprising Formulas (VI), (VII), and (VIII), are described above insection (II)(a).

The first step of this process comprises heating the reactants in thepresence or absence of an acid catalyst. Suitable acid catalysts andsuitable amounts are detailed above in section (II)(a). In someembodiments, the heating step is performed under a vacuum. The heatingstep may be performed in the presence of a solvent, as detailed above,or the heating may be performed in the absence of a solvent (i.e.,neat). Similar to the method detailed above, the reaction mixture may beheated to and maintained at a temperature ranging from about 100° C. toabout 200° C. In exemplary embodiments, the reaction mixture may beheated to about 130° C. to about 160° C. The duration of the heatingstep may also vary. In some embodiments, the duration of the heatingstep may range from about 2 hours to about 10 hours, or from about 3hours to about 5 hours.

The second step of this process comprises additional heating at a highertemperature and under reduced pressure (i.e., thermal cracking). Thetemperature of the second step may range from about 150° C. to about250° C. In some embodiments the temperature of the second step may range150° C. to about 180° C., from about 180° C. to about 200° C., fromabout 200° C. to about 220° C., or from about 220° C. to about 250° C.In general, the second step is performed under a vacuum. The pressure ofthe reaction may be less than about 10 Torr, less than about 1 Torr,less than about 500 mTorr, or less than about 200 mTorr. In variousembodiments, the pressure of the second step of the reaction may rangefrom about 200 mTorr to about 500 mTorr, or may range from about 0.5Torr to about 1 Torr. The duration of the second step of the process mayrange from about 1 hour to about 5 hours. In one embodiment, theduration of the second step of the process may range from about 2 hoursto about 3 hours. During the second step of the process, the compoundcomprising Formula (IX) may be distilled as detailed above in section(II)(a).

The yield of the compound comprising Formula (IX) prepared by thepolymerization/thermal cracking process can and will vary depending upona variety of factors. In various embodiments, the yield of the compoundcomprising Formula (IX) in distillates from the reaction mixture may beat least about 15%, at least about 20%, at least about 30%, at leastabout 40%, at least about 50%, at least about 60%, at least about 70%,at least about 80%, at least about 90%, at least about 95%, or at leastabout 99%.

The compound comprising Formula (IX) may be isolated from the reactionmixture and/or purified by means including by size exclusionchromatography, HPLC, ion-exchange chromatography, chiralchromatography, other types of chromatography, precipitation,distillation, or crystallization.

(c) Preparation of Compounds Comprising Formula (IV)

The method for preparing the compound comprising Formula (IV) comprisescontacting a compound comprising Formula (X) and a compound comprisingFormula (XI) according to Reaction Scheme 2:

wherein,

-   -   R⁶ and R¹⁰ are independently chosen from hydrogen, hydrocarbyl,        and substituted hydrocarbyl,    -   R⁷ and R¹¹ are optionally present, when present each is        independently chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   Y and Z are independently chosen from sulfone, sulfoxide, and        selenium; and    -   n and m are integers ≧1.

In general, the compound comprising Formula (IV) may be produced bysubjecting compounds comprising Formulas (X) and (XI) to conditions suchthat the compounds form a cyclic dimer. R⁶, R⁷, R¹⁰, R¹¹, Y, Z, n and mof the compounds comprising Formulas (X), (XI), and (IV) may generallybe as set out in Section (I).

The compounds comprising Formulas (X) and (XI) may be provided to thereaction in an approximately equal molar ratio. In some embodiments, thecompounds comprising Formulas (X) and (XI) may be provided in a molarratio of about 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1; 0.7:1, 0.8:1,0.9:1, 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8,1:2.0, 1:2.5, 1:3, or 1:3.5. In a preferred embodiment, the compoundscomprising Formulas (X) and (XI) are provided in an equal molar ratio.

A variety of acid catalysts may be used in the reaction. In someembodiments, the acid catalyst may be chosen from organic acids,inorganic acids, and solid resins. Exemplary acid catalysts include,without limitation, acetic acid, hydrochloric acid, trifluoroaceticacid, methanesulfonic acid, ortho- meta- and para-toluenesulfonic acid,sulfuric acid, phosphoric acid, xylenesulfonic acid, Dowex resins,Amberlyst resins, Zn dust, and Sn dust.

The acid catalyst may be added in a range of ratios to the compoundscomprising Formulas (X) and (XI). In some aspects the amount of catalystadded ranges from about 0.0001 mol % of the amount of the compoundscomprising Formulas (X) and (XI) to about 5 mol % of the compoundscomprising Formulas (X) and (XI). In some embodiments, the acid catalystmay be added in an amount below 5 mol %, below 2 mol %, or below 1 mol%. More preferably, the acid catalyst may be provided in the reaction ina molar ratio of about 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007,0.008, 0.009, or 0.010 mol % to the compounds comprising Formulas (X)and (XI).

The temperature at which the reaction takes place may vary in differentembodiments and/or over the course of the reaction. In some aspects, thereaction may be conducted at a temperature of 100° C., 110° C., 120° C.,130° C., 140° C., 150° C., 160° C., 170° C., 180° C., 190° C., 200° C.,or at a range between and including any two of these values. In oneembodiment, the reaction may be carried out at a temperature rangingfrom about 100° C. and about 200° C. In another embodiment, thetemperature may range from about 130° C. and about 150° C. In general,the reaction is conducted at atmospheric pressure, but in certainembodiments, the reaction may also be conducted above or belowatmospheric pressure.

The process may be performed in the presence of a solvent, while inother aspects the reaction may be performed neat. Where a solvent ispresent, the solvent may be chosen, by way of non-limiting example, fromthe solvents listed in section (II)(a). In one embodiment, the solventis chosen from toluene, xylene, anisole, and mixtures thereof.

The weight-to-weight ratio of the solvent to the compounds comprisingFormulas (X) and (XI) can and will vary. Typically, the weight-to-weightratio of the solvent to the compounds comprising Formulas (X) and (XI)may range from about 1:1 to about 100:1. In various embodiments, theweight-to-weight ratio of the solvent to the compounds comprisingFormulas (X) and (XI) may range from about 1:1 to 5:1, from about 5:1 toabout 20:1, from about 20:1 to about 40:1, from about 40:1 to about80:1, or from about 80:1 to about 100:1

The duration of the reaction can and will vary. In general, the reactionmay be allowed to proceed from several hours to several days. Typically,however, the reaction is allowed to proceed for a sufficient period oftime until the reaction is complete, as determined by means well knownto those of skill in the art. In this context, the final reactionmixture contains a significantly diminished amount of the compoundscomprising Formulas (X) and (XI) and a significantly increased amount ofthe compound comprising Formula (IV) compared to the amounts of eachpresent at the beginning of the reaction. In some embodiments, thereaction may be allowed to proceed for a period of time ranging fromabout 1 hour to about 10 hours.

The yield of the compound comprising Formula (IV) can and will vary. Ingeneral, yield of the compound comprising Formula (IV) will be at leastabout 15%, at least about 20%, 30%, at least about 40%, at least about50%, at least about 60%, at least about 70%, at least about 80%, or atleast about 90%.

(d) Preparation of the Compound Comprising Formula (V)

In one embodiment, a process for producing the compound comprisingFormula (V) is provided, which proceeds according to Reaction Scheme 3:

In exemplary embodiments, the acid catalyst is p-toluenesulfonic acid.The compound comprising Formula (VIb) is heated to 110-115° C. in thepresence of the acid catalyst in toluene for 3-5 hours with continuousremoval of water using a Dean Stark trap.

In some embodiments, the process provides the compound comprisingFormula (V) as a racemic mixture comprising stereoisomers of thecompound comprising Formula (V) (i.e., D-, L-, and meso isomers; seecompounds 2, 3, and 4, respectively, in Table 5). The racemic mixturemay be separated into individual diastereomers of the compoundcomprising Formula (V). In some embodiments, the D-, and L-isomers maybe first separated from the meso isomer by methods known in the artincluding, but not limited to, recrystallization, distillation, andchromatography. The D- and L-isomers may then be separated by meansknown in the art including, but not limited to, chiral chromatography,recrystallization, and distillation. In other embodiments, the D-, L-,and meso isomers may be separated by chiral chromatography (see Example4).

(III) Applications

The cyclic dimer compounds detailed above in section (I) may be used ina variety of applications. Suitable applications include, without limit,use as plasticizers, emulsifiers, additives, processing aids, nutritiveagents, antioxidant agents, antimicrobial agents, anticorrosive agents,and feed additives.

In some embodiments, the cyclic dimer compounds may be used as a sourceof alpha acids. In some embodiments, the compounds disclosed herein maybe used as feed additives or included in feed compositions or feedpremixes. In other embodiments, the compounds described above in section(I) may be part of a composition comprising at least one nutritiveand/or pharmaceutical agent.

The compositions comprising the cyclic dimer compounds may beadministered to human or animal subjects. Non-limiting examples ofsuitable animal subjects include companion animals such as cats, dogs,rabbits, horses, and rodents such as gerbils; agricultural animals suchas cows, dairy cows, dairy calves, beef cattle, pigs, goats, sheep,horses, deer; zoo animals such as primates, elephants, zebras, largecats, bears, and the like; research animals such as rabbits, sheep,pigs, dogs, primates, mice, rats and other rodents; avians, includingbut not limited to chickens, ducks, turkeys, ostrich, and emu; andaquatic animals chosen from fish and crustaceans including, but notlimited to, salmon, shrimp, carp, tilapia, and shell fish. The subjectmay be monogastric or a ruminant. When the subject is a ruminant thecompounds described in section (I) may remain substantially intact inthe rumen such that the compound is not broken down in the rumen. Thus,the feed composition may have an increased digestional efficiency forruminant subjects. In some aspects, the compounds described in section(I) remain substantially intact in the rumen. In other aspects, thecompounds described in section (I) may hydrolyze after passage throughthe rumen.

(IV) Compositions Comprising Cyclic Dimers

In yet another aspect, the present invention provides compositionscomprising at least one cyclic dimer compound detailed above in section(I). The compositions may further comprise at least one nutritive and/orpharmaceutical agent.

(a) Feed Compositions

In some embodiments, the composition may be a feed composition or a feedpremix. The feed composition comprises one or more of the compoundsdescribed in section (I) and at least one nutritive agent. The nutritiveagent may be a hydrolysis product of the cyclic dimer. The compoundsdescribed in section (I) may hydrolyze after passage from through thestomach or rumen of a subject. For example, the compounds in section (I)may hydrolyze under conditions where the compounds are subjected to a pHof about 4.5, 4.0, 3.5, 3.0, 2.5, 2.0, 1.5, 1.0, or 0.5, or any pHbetween and including the listed values. A substantially hydrolyzedcomposition, as used herein, refers to a solution where greater than 50%of the compounds in section (I) of the composition are in a noncyclicalform. In some embodiments, substantially hydrolyzed refers to greaterthan 60%, or greater than 70%, or greater than 80%, or greater than 90%hydrolyzed.

In other embodiments, the nutritive agent may be a carbohydrate source,a fat source, a protein source, an amino acid, and alpha hydroxy acid,or combinations thereof. Suitable carbohydrate sources may be chosenfrom those known in the art and include, without limitation, alginate,arrowroot, barley, canola, cassava, corn, corn syrup, cottonseed meal,fructose, glucose, galactose, grain sorghum, kelp meal, lactose, maize,maltose, mannose, potatoes, oats, rice, rye, sago, sorbitol, soybeans,tapioca, wheat, wheat gluten, yam, and combinations thereof.

The fat source may be an inert fat or a non-inert fat. Non-limitingexamples of non-inert fats include plant derived oils (e.g., canola oil,corn oil, cottonseed oil, palm oil, peanut oil, safflower oil, soybeanoil, and sunflower oil), fish oils (e.g., menhaden oil, anchovy oil,albacore tuna oil, cod liver oil, herring oil, lake trout oil, mackereloil, salmon oil, and sardine oil), animal fats (e.g., poultry fat, beeftallow, butter, pork lard, and whale blubber), yellow grease (i.e.,waste grease from restaurants and low-grade fats from rendering plants),and combinations thereof. The non-inert fat source may also be a highfat product such as fish meal (e.g., menhaden meal, anchovy meal,herring meal, pollack meal, salmon meal, tuna meal, and whitefish meal),oilseeds (e.g., canola seeds, cottonseeds, flax seeds, linseeds, Nigerseeds, sesame seeds, soy beans, and sunflower seeds), or distillersgrains (e.g., dried distillers grains and solubles (DDGS) and wetdistillers grains). The fat source may be a ruminally inert fat.Suitable examples of ruminally inert fats include calcium salts of palmfatty acids (e.g., MEGALAC®), saturated free fatty acids, orhydrogenated tallow (e.g., ALIFET®).

Suitable protein sources may be animal-derived proteins, plant-derivedproteins, or combinations thereof. In some embodiments, suitable sourcesof animal derived protein include blood meal, bone meal, fish meal, fishprocessing by-products, meat meal, meat and bone meal, poultryby-produce meal, feather meal, and combinations thereof. In otherembodiments, suitable sources of plant-derived proteins include grainssuch as corn, oats, soybean, and the like; grain protein concentratessuch as soy protein concentrate; legumes such as peas, lupine, alfalfa;distiller's grains; oilseed meals such as canola meal, cottonseed meal,flaxseed meal, soybean meal, sunflower seed meal; and combinationsthereof.

In some embodiments, the feed composition/premix may include one or morealpha acids including amino acids and alpha hydroxy acids. Suitableexamples of amino acids, depending upon the formulation, includealanine, arginine, asparagines, aspartate, cysteine, glutamate,glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine,selenomethionine, phenylalanine, proline, serine, threonine, tryptophan,tyrosine, and valine. Other amino acids usable as feed additivesinclude, by way of non-limiting example, N-acylamino acids, hydroxyhomologue compounds, and physiologically acceptable salts thereof, suchas hydrochlorides, hydrosulfates, ammonium salts, potassium salts,calcium salts, magnesium salts and sodium salts of amino acids. The feedcompositions may further include an alpha hydroxy acid. In some aspectsthe alpha hydroxy acids are alpha hydroxy analogs of amino acids. In oneaspect, the alpha acid is the hydroxy analog of methionine.

The feed composition may be formulated as a liquid, an emulsion, drypellets, or a powder, and may be mixed with various other ingredients.

(b) Combinations with Nutritive and/or Pharmaceutical Agents

In other embodiments, the composition comprises at least one compounddetailed in section (I) in combination with at least one nutritiveand/or pharmaceutical agent. Nutritive agents may comprise any agentthat provides nutritive value when administered to a subject.Non-limiting examples of nutritive agents include vitamins, minerals(e.g., organic or inorganic), antioxidants, organic acids, polyunsaturated fatty acids (“PUFA”), prebiotics, probiotics, herbs, andpigments.

Suitable vitamins include vitamin C, vitamin A, vitamin E, vitamin B12,vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid,pyridoxine, thiamine, pantothenic acid, and biotin. The form of thevitamin may include salts of the vitamin, derivatives of the vitamin,compounds having the same or similar activity of a vitamin, andmetabolites of a vitamin.

Suitable organic trace mineral may comprise a metal chelate comprisingmetal ions and an amino acid ligand. Alternatively, the organic tracemineral may be a metal salt comprising metal ions and an amino acidanion. The metal ions may be selected from the group consisting of zincions, copper ions, manganese ions, iron ions, chromium ions, cobaltions, magnesium ions, calcium ions, and combinations thereof. In apreferred embodiment, the metal ions are zinc ions, manganese ions, andcopper ions. The amino acids may be selected from the group comprisingalanine, arginine, asparagine, aspartic acid, cysteine, glutamine,glutamic acid, glycine, histidine, isoleucine, leucine, lysine,methionine, phenylalanine, proline, serine, threonine, tryptophan,tyrosine, and valine, or their hydroxy analogs. In certain embodiments,the copper and zinc ions are preferably divalent, i.e., each ion carriesa charge of 2⁺. The molar ratio of amino acids to metal ions in thechelate molecule may generally vary from 1:1 to 3:1 or higher.Typically, a metal chelate may comprise a mixture of 1:1, 2:1 and 3:1species. Preferably, the molar ratio of amino acids to metal ion in thechelate molecule may generally vary from 1.5:1 to 2.5:1. In an aqueousmedium, the relative proportions of these species are determined by theapplicable stability constants. Where the number of ligands equates tothe charge on the metal ion, the charge is typically balanced becausethe carboxyl moieties of the amino acids are in deprotonated form. Forexample, in the chelate species wherein the metal cation carries acharge of 2+ and the amino acid to metal ratio is 2:1, each of thehydroxy or amino groups is understood to be bound by a coordinatecovalent bond to the metal ion. Where the number of ligands exceeds thecharge on the metal ion, e.g., in a 3:1 chelate of a divalent metal ion,the amino acids in excess of the charge typically may remain in aprotonated state to balance the charge. On the other hand, where thepositive charge on the metal ion exceeds the number of amino acids, thecharge may be balanced by the presence of another anion such as, forexample, chloride, bromide, iodide, bicarbonate, hydrogen sulfate,dihydrogen phosphate and combinations thereof. Divalent anions may alsobe present. In an exemplary embodiment, the metal chelate comprises2-hydroxy-4-methylthiobutanoic acid.

The mineral may also be an inorganic trace mineral. Suitable inorganictrace minerals include, for example, metal sulfates, metal oxides, metalcarbonates, and metal halides. By way of non-limiting example, theinorganic trace mineral may be copper sulfate, copper oxide, copperchloride, or copper carbonate. Alternatively, the inorganic tracemineral may be manganese sulfate, manganese chloride, or manganousoxide. In another embodiment, the inorganic trace mineral may be zincsulfate, zinc oxide, zinc chloride, or zinc carbonate. In yet anadditional embodiment, the inorganic trace mineral may be sodiumselenite or sodium selenate.

Suitable antioxidants include, but are not limited to, ascorbic acid andits salts, ascorbyl palmitate, ascorbyl stearate, anoxomer,n-acetylcysteine, benzyl isothiocyanate, m-aminobenzoic acid,o-aminobenzoic acid, p-aminobenzoic acid (PABA), butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid,canthaxantin, alpha-carotene, beta-carotene, beta-caraotene,beta-apo-carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate,chlorogenic acid, citric acid and its salts, clove extract, coffee beanextract, p-coumaric acid, 3,4-dihydroxybenzoic acid,N,N′-diphenyl-p-phenylenediamine (DPPD), dilauryl thiodipropionate,distearyl thiodipropionate, 2,6-di-tert-butylphenol, dodecyl gallate,edetic acid, ellagic acid, erythorbic acid, sodium erythorbate,esculetin, esculin, 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline(ethoxyquin), ethyl gallate, ethyl maltol, ethylenediaminetetraaceticacid (EDTA), eucalyptus extract, eugenol, ferulic acid, flavonoids(e.g., catechin, epicatechin, epicatechin gallate, epigallocatechin(EGO), epigallocatechin gallate (EGCG), polyphenolepigallocatechin-3-gallate, flavones (e.g., apigenin, chrysin,luteolin), flavonols (e.g., datiscetin, myricetin, daemfero),flavanones, fraxetin, fumaric acid, gallic acid, gentian extract,gluconic acid, glycine, gum guaiacum, hesperetin, alpha-hydroxybenzylphosphinic acid, hydroxycinammic acid, hydroxyglutaric acid,hydroquinone, n-hydroxysuccinic acid, hydroxytryrosol, hydroxyurea, ricebran extract, lactic acid and its salts, lecithin, lecithin citrate;R-alpha-lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxytryptamine, methyl gallate, monoglyceride citrate; monoisopropylcitrate; morin, beta-naphthoflavone, nordihydroguaiaretic acid (NDGA),octyl gallate, oxalic acid, palmityl citrate, phenothiazine,phosphatidylcholine, phosphoric acid, phosphates, phytic acid,phytylubichromel, pimento extract, propyl gallate, polyphosphates,quercetin, trans-resveratrol, rosemary extract, rosmarinic acid, sageextract, sesamol, silymarin, sinapic acid, succinic acid, stearylcitrate, syringic acid, tartaric acid, thymol, tocopherols (i.e.,alpha-, beta-, gamma- and delta-tocopherol), tocotrienols (i.e., alpha-,beta-, gamma- and delta-tocotrienols), tyrosol, vanilic acid,2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., lonox 100),2,4-(tris-3′,5′-bi-tert-butyl-4′-hydroxybenzyl)-mesitylene (i.e., lonox330), 2,4,5-trihydroxybutyrophenone, ubiquinone, tertiary butylhydroquinone (TBHQ), thiodipropionic acid, trihydroxy butyrophenone,tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10,wheat germ oil, zeaxanthin, or combinations thereof.

A variety of organic acids comprised of carboxylic acids are suitable.In one embodiment, the organic acid may contain from about one to abouttwenty-five carbon atoms. In another embodiment, the organic acid mayhave from about three to about twenty-two carbon atoms. In a furtherembodiment, the organic acid may contain from about three to abouttwelve carbon atoms. In yet another embodiment, the organic acid maycontain from about eight to about twelve carbon atoms. In still anotherembodiment, the organic acid may contain from about two to about sixcarbon atoms. Suitable organic acids, by way of non-limiting example,include formic acid, acetic acid, propionic acid, butanoic acid, benzoicacid, lactic acid, malic acid, tartaric acid, mandelic acid, citricacid, fumaric acid, sorbic acid, boric acid, succinic acid, adipic acid,glycolic acid, cinnamaldehyde, and glutaric acid.

Salts of organic acids comprising carboxylic acids are also suitable forcertain embodiments. Representative suitable salts include the ammonium,magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper,and zinc salts of organic acids. In one embodiment, the organic acid isan ammonium, magnesium, calcium, lithium, sodium, potassium, selenium,iron, copper, or zinc salt of formic acid. In another embodiment, theorganic acid is an ammonium, magnesium, calcium, lithium, sodium,potassium, selenium, iron, copper, or zinc salt of acetic acid. In yetanother embodiment, the organic acid is an ammonium, magnesium, calcium,lithium, sodium, potassium, selenium, iron, copper, or zinc salt ofpropionic acid. In an additional embodiment, the organic acid is anammonium, magnesium, calcium, lithium, sodium, potassium, selenium,iron, copper, or zinc salt of butanoic acid. In a further embodiment,the organic acid is an ammonium, magnesium, calcium, lithium, sodium,potassium, selenium, iron, copper, or zinc salt of benzoic acid. Instill another embodiment, the organic acid is an ammonium, magnesium,calcium, lithium, sodium, potassium, selenium, iron, copper, or zincsalt of lactic acid. In yet another embodiment, the organic acid is anammonium, magnesium, calcium, lithium, sodium, potassium, selenium,iron, copper, or zinc salt of malic acid. In still another embodiment,the organic acid is an ammonium, magnesium, calcium, lithium, sodium,potassium, selenium, iron, copper, or zinc salt of tartaric acid. In afurther embodiment, the organic acid is an ammonium, magnesium, calcium,lithium, sodium, potassium, selenium, iron, copper, or zinc salt ofmandelic acid. In yet another embodiment, the organic acid is anammonium, magnesium, calcium, lithium, sodium, potassium, selenium,iron, copper, or zinc salt of citric acid. In an additional embodiment,the organic acid is an ammonium, magnesium, calcium, lithium, sodium,potassium, selenium, iron, copper, or zinc salt of fumaric acid. In anadditional embodiment, the organic acid is an ammonium, magnesium,calcium, lithium, sodium, potassium, selenium, iron, copper, or zincsalt of sorbic acid. In another embodiment, the organic acid is anammonium, magnesium, calcium, lithium, sodium, potassium, selenium,iron, copper, or zinc salt of boric acid. In yet another embodiment, theorganic acid is an ammonium, magnesium, calcium, lithium, sodium,potassium, selenium, iron, copper, or zinc salt of succinic acid. Inanother embodiment, the organic acid is an ammonium, magnesium, calcium,lithium, sodium, potassium, selenium, iron, copper, or zinc salt ofadipic acid. In yet another embodiment, the organic acid is an ammonium,magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper,or zinc salt of glycolic acid. In an additional embodiment, the organicacid is an ammonium, magnesium, calcium, lithium, sodium, potassium,selenium, iron, copper, or zinc salt of glutaric acid.

Alternatively, the organic acid may be comprised of a substitutedcarboxylic acid. A substituted carboxylic acid generally has the samefeatures as those detailed above for carboxylic acids, but thehydrocarbyl chain has been modified such that it is branched, is part ofa ring structure, or contains some other substitution. In oneembodiment, the substituted carboxylic acid may contain one or moreadditional carboxyl groups. Saturated dicarboxylic acids include malonicacid, succinic acid, glutaric acid, and adipic acid, and unsaturateddicarboxylic acids include maleic acid and fumaric acid. In anotherembodiment, the substituted carboxylic acid may contain one or morehydroxy groups. A substituted carboxylic acid with a hydroxy group onthe alpha carbon, i.e., the carbon adjacent to the carboxyl carbon, isgenerally called a α-hydroxy carboxylic acid. Examples of suitableα-hydroxy carboxylic acids include glycolic acid, lactic acid, malicacid, and tartaric acid. In an alternate embodiment, the substitutedcarboxylic acid may contain one or more carbonyl groups. In yet anotherembodiment, the substituted carboxylic acid may contain an amino groupon the alpha carbon, i.e., is an α-amino acid. In one embodiment, theα-amino acid may be one of the twenty standard amino acids orderivatives thereof. In another embodiment, the α-amino acid may be anessential α-amino acid selected from the group consisting of arginine,histidine, isoleucine, leucine, lysine, methionine, phenylalanine,threonine, tryptophan, and valine. Salts of organic acids comprisingsubstituted carboxylic acids are also suitable for certain embodiments.Representative suitable salts include the ammonium, magnesium, calcium,lithium, sodium, potassium, selenium, iron, copper, and zinc salts oforganic acids comprising substituted carboxylic acids.

Suitable PUFAs include a long chain fatty acid with at least 18 carbonatoms and at least two carbon-carbon double bonds, generally in thecis-configuration. In an exemplary embodiment, the PUFA is an omegafatty acid. The PUFA may be an omega-3 fatty acid in which the firstdouble bond occurs in the third carbon-carbon bond from the methyl endof the carbon chain (i.e., opposite the carboxyl acid group). Suitableexamples of omega-3 fatty acids include all-cis 7,10,13-hexadecatrienoicacid; all-cis-9,12,15-octadecatrienoic acid (alpha-linolenic acid, ALA);all-cis-6,9,12,15,-octadecatetraenoic acid (stearidonic acid);all-cis-8,11,14,17-eicosatetraenoic acid (eicosatetraenoic acid);all-cis-5,8,11,14,17-eicosapentaenoic acid (eicosapentaenoic acid, EPA);all-cis-7,10,13,16,19-docosapentaenoic acid (clupanodonic acid, DPA);all-cis-4,7,10,13,16,19-docosahexaenoic acid (docosahexaenoic acid,DHA); all-cis-4,7,10,13,16,19-docosahexaenoic acid; andall-cis-6,9,12,15,18,21-tetracosenoic acid (nisinic acid). In analternative embodiment, the PUFA may be an omega-6 fatty acid in whichthe first double bond occurs in the sixth carbon-carbon bond from themethyl end of the carbon chain. Examples of omega-6 fatty acids includeall-cis-9,12-octadecadienoic acid (linoleic acid);all-cis-6,9,12-octadecatrienoic acid (gamma-linolenic acid, GLA);all-cis-11,14-eicosadienoic acid (eicosadienoic acid);all-cis-8,11,14-eicosatrienoic acid (dihomo-gamma-linolenic acid, DGLA);all-cis-5,8,11,14-eicosatetraenoic acid (arachidonic acid, AA);all-cis-13,16-docosadienoic acid (docosadienoic acid);all-cis-7,10,13,16-docosatetraenoic acid (adrenic acid); andall-cis-4,7,10,13,16-docosapentaenoic acid (docosapentaenoic acid). Inyet another alternative embodiment, the PUFA may be an omega-9 fattyacid in which the first double bond occurs in the ninth carbon-carbonbond from the methyl end of the carbon chain, or a conjugated fattyacid, in which at least one pair of double bonds are separated by onlyone single bond. Suitable examples of omega-9 fatty acids includecis-9-octadecenoic acid (oleic acid); cis-11-eicosenoic acid (eicosenoicacid); all-cis-5,8,11-eicosatrienoic acid (mead acid); cis-13-docosenoicacid (erucic acid), and cis-15-tetracosenoic acid (nervonic acid).Examples of conjugated fatty acids include 9Z,11E-octadeca-9,11-dienoicacid (rumenic acid); 10E,12Z-octadeca-9,11-dienoic acid;8E,10E,12Z-octadecatrienoic acid (α-calendic acid);8E,10E,12E-octadecatrienoic acid (β-Calendic acid);8E,10Z,12E-octadecatrienoic acid (jacaric acid);9E,11E,13Z-octadeca-9,11,13-trienoic acid (α-eleostearic acid);9E,11E,13E-octadeca-9,11,13-trienoic acid (β-eleostearic acid);9Z,11Z,13E-octadeca-9,11,13-trienoic acid (catalpic acid), and9E,11Z,13E-octadeca-9,11,13-trienoic acid (punicic acid).

Probiotics and prebiotics may include yeast and bacteria that helpestablish an immune protective rumen or gut microflora as well as smalloligosaccharides. By way of non-limiting example, yeast-derivedprobiotics and prebiotics include yeast cell wall derived componentssuch as β-glucans, arabinoxylan isomaltose, agarooligosaccharides,lactosucrose, cyclodextrins, lactose, fructooligosaccharides,laminariheptaose, lactulose, β-galactooligosaccharides,mannanoligosaccharides, raffinose, stachyose, oligofructose, glucosylsucrose, sucrose thermal oligosaccharide, isomalturose, caramel, inulin,and xylooligosaccharides. In an exemplary embodiment, the yeast-derivedagent may be β-glucans and/or mannanoligosaccharides. Sources for yeastcell wall derived components include Saccharomyces bisporus,Saccharomyces boulardii, Saccharomyces cerevisiae, Saccharomycescapsularis, Saccharomyces delbrueckii, Saccharomyces fermentati,Saccharomyces lugwigii, Saccharomyces microellipsoides, Saccharomycespastorianus, Saccharomyces rosei, Candida albicans, Candida cloaceae,Candida tropicalis, Candida utilis, Geotrichum candidum, Hansenulaamericana, Hansenula anomala, Hansenula wingei, and Aspergillus oryzae.

Probiotics and prebiotics may also include bacteria cell wall derivedagents such as peptidoglycan and other components derived fromgram-positive bacteria with a high content of peptidoglycan. Exemplarygram-positive bacteria include Lactobacillus acidophilus, Bifedobactthermophilum, Bifedobat longhum, Streptococcus faecium, Bacilluspumilus, Bacillus subtilis, Bacillus licheniformis, Lactobacillusacidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacteriumbifidium, Propionibacterium acidipropionici, Propionibacteriiumfreudenreichii, and Bifidobacterium pscudolongum.

Suitable herbals and herbal derivatives, as used herein, refer to herbalextracts, and substances derived from plants and plant parts, such asleaves, flowers and roots, without limitation. Non-limiting exemplaryherbals and herbal derivatives include agrimony, alfalfa, aloe vera,amaranth, angelica, anise, barberry, basil, bayberry, bee pollen, birch,bistort, blackberry, black cohosh, black walnut, blessed thistle, bluecohosh, blue vervain, boneset, borage, buchu, buckthorn, bugleweed,burdock, capsicum, cayenne, caraway, cascara sagrada, catnip, celery,centaury, chamomile, chaparral, chickweed, chicory, chinchona, cloves,coltsfoot, comfrey, cornsilk, couch grass, cramp bark, culver's root,cyani, cornflower, damiana, dandelion, devils claw, dong quai,echinacea, elecampane, ephedra, eucalyptus, evening primrose, eyebright,false unicorn, fennel, fenugreek, figwort, flaxseed, garlic, gentian,ginger, ginseng, golden seal, gotu kola, gum weed, hawthorn, hops,horehound, horseradish, horsetail, hoshouwu, hydrangea, hyssop, icelandmoss, irish moss, jojoba, juniper, kelp, lady's slipper, lemon grass,licorice, lobelia, mandrake, marigold, marjoram, marshmallow, mistletoe,mullein, mustard, myrrh, nettle, oatstraw, oregon grape, papaya,parsley, passion flower, peach, pennyroyal, peppermint, periwinkle,plantain, pleurisy root, pokeweed, prickly ash, psyllium, quassia, queenof the meadow, red clover, red raspberry, redmond clay, rhubarb, rosehips, rosemary, rue, safflower, saffron, sage, St. John's wort,sarsaparilla, sassafras, saw palmetto, scullcap, senega, senna,shepherd's purse, slippery elm, spearmint, spikenard, squawvine,stillingia, strawberry, taheebo, thyme, uva ursi, valerian, violet,watercress, white oak bark, white pine bark, wild cherry, wild lettuce,wild yam, willow, wintergreen, witch hazel, wood betony, wormwood,yarrow, yellow dock, yerba santa, yucca and combinations thereof.

Suitable non-limiting pigments include actinioerythrin, alizarin,alloxanthin, β-apo-2′-carotenal, apo-2-lycopenal, apo-6′-lycopenal,astacein, astaxanthin, azafrinaldehyde, aacterioruberin, aixin,α-carotine, β-carotine, γ-carotine, β-carotenone, canthaxanthin,capsanthin, capsorubin, citranaxanthin, citroxanthin, crocetin,crocetinsemialdehyde, crocin, crustaxanthin, cryptocapsin,α-cryptoxanthin, β-cryptoxanthin, cryptomonaxanthin, cynthiaxanthin,decaprenoxanthin, dehydroadonirubin, diadinoxanthin,1,4-diamino-2,3-dihydroanthraquinone, 1,4-dihydroxyanthraquinone,2,2′-Diketospirilloxanthin, eschscholtzxanthin, eschscholtzxanthone,flexixanthin, foliachrome, fucoxanthin, gazaniaxanthin,hexahydrolycopene, hopkinsiaxanthin, hydroxyspheriodenone,isofucoxanthin, loroxanthin, lutein, luteoxanthin, lycopene,lycopersene, lycoxanthin, morindone, mutatoxanthin, neochrome,neoxanthin, nonaprenoxanthin, OH-Chlorobactene, okenone, oscillaxanthin,paracentrone, pectenolone, pectenoxanthin, peridinin, phleixanthophyll,phoeniconone, phoenicopterone, phoenicoxanthin, physalien, phytofluene,pyrrhoxanthininol, quinones, rhodopin, rhodopinal, rhodopinol,rhodovibrin, rhodoxanthin, rubixanthone, saproxanthin,semi-α-carotenone, semi-β-carotenone, sintaxanthin, siphonaxanthin,siphonein, spheroidene, tangeraxanthin, torularhodin, torularhodinmethyl ester, torularhodinaldehyde, torulene,1,2,4-trihydroxyanthraquinone, triphasiaxanthin, trollichrome,vaucheriaxanthin, violaxanthin, wamingone, xanthin, zeaxanthin,α-zeacarotene and combinations thereof.

Suitable non-limiting pharmaceutically acceptable agents include anacid/alkaline-labile drug, a pH dependent drug, or a drug that is a weakacid or a weak base. Examples of acid-labile drugs include statins(e.g., pravastatin, fluvastatin and atorvastatin), antiobiotics (e.g.,penicillin G, ampicillin, streptomycin, erythromycin, clarithromycin andazithromycin), nucleoside analogs [e.g., dideoxyinosine (ddI ordidanosine), dideoxyadenosine (ddA), dideoxycytosine (ddC)], salicylates(e.g., aspirin), digoxin, bupropion, pancreatin, midazolam, andmethadone. Drugs that are only soluble at acid pH include nifedipine,emonapride, nicardipine, amosulalol, noscapine, propafenone, quinine,dipyridamole, josamycin, dilevalol, labetalol, enisoprost, andmetronidazole. Drugs that are weak acids include phenobarbital,phenyloin, zidovudine (AZT), salicylates (e.g., aspirin), propionic acidcompounds (e.g., ibuprofen), indole derivatives (e.g., indomethacin),fenamate compounds (e.g., meclofenamic acid), pyrrolealkanoic acidcompounds (e.g., tolmetin), cephalosporins (e.g., cephalothin,cephalaxin, cefazolin, cephradine, cephapirin, cefamandole, andcefoxitin), 6-fluoroquinolones, and prostaglandins. Drugs that are weakbases include adrenergic agents (e.g., ephedrine, desoxyephedrine,phenylephrine, epinephrine, salbutamol, and terbutaline), cholinergicagents (e.g., physostigmine and neostigmine), antispasmodic agents(e.g., atropine, methantheline, and papaverine), curariform agents(e.g., chlorisondamine), tranquilizers and muscle relaxants (e.g.,fluphenazine, thioridazine, trifluoperazine, chlorpromazine, andtriflupromazine), antidepressants (e.g., amitriptyline andnortriptyline), antihistamines (e.g., diphenhydramine, chlorpheniramine,dimenhydrinate, tripelennamine, perphenazine, chlorprophenazine, andchlorprophenpyridamine), cardioactive agents (e.g., verapamil,diltiazem, gallapomil, cinnarizine, propranolol, metoprolol andnadolol), antimalarials (e.g., chloroquine), analgesics (e.g.,propoxyphene and meperidine), antifungal agents (e.g., ketoconazole anditraconazole), antimicrobial agents (e.g., cefpodoxime, proxetil, andenoxacin), caffeine, theophylline, and morphine. In another embodiment,the drug may be a biphosphonate or another drug used to treatosteoporosis. Non-limiting examples of a biphosphonate includealendronate, ibandronate, risedronate, zoledronate, pamidronate,neridronate, olpadronate, etidronate, clodronate, and tiludronate. Othersuitable drugs include estrogen, selective estrogen receptor modulators(SERMs), and parathyroid hormone (PTH) drugs. In yet another embodiment,the drug may be an antibacterial agent. Suitable antibiotics includeaminoglycosides (e.g., amikacin, gentamicin, kanamycin, neomycin,netilmicin, streptomycin, and tobramycin), carbecephems (e.g.,loracarbef) a carbapenem (e.g., certapenem, imipenem, and meropenem),cephalosporins (e.g., cefadroxil cefazolin, cephalexin, cefaclor,cefamandole, cephalexin, cefoxitin, cefprozil, cefuroxime, cefixime,cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime,ceftazidime, ceftibuten, ceftizoxime, and ceftriaxone), macrolides(e.g., azithromycin, clarithromycin, dirithromycin, erythromycin, andtroleandomycin), monobactam, penicillins (e.g., amoxicillin, ampicillin,carbenicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin,penicillin G, penicillin V, piperacillin, and ticarcillin), polypeptides(e.g., bacitracin, colistin, and polymyxin B), quinolones (e.g.,ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin,moxifloxacin, norfloxacin, ofloxacin, and trovafloxacin), sulfonamides(e.g., mafenide, sulfacetamide, sulfamethizole, sulfasalazine,sulfisoxazole, and trimethoprim-sulfamethoxazole), and tetracyclines(e.g., demeclocycline, doxycycline, minocycline, and oxytetracycline).In an alternate embodiment, the drug may be an antiviral proteaseinhibitor (e.g., amprenavir, fosamprenavir, indinavir,lopinavir/ritonavir, ritonavir, saquinavir, and nelfinavir). In a stillanother embodiment, the drug may be a cardiovascular drug. Examples ofsuitable cardiovascular agents include cardiotonic agents (e.g.,digitalis (digoxin), ubidecarenone, and dopamine), vasodilating agents(e.g., nitroglycerin, captopril, dihydralazine, diltiazem, andisosorbide dinitrate), antihypertensive agents (e.g., alpha-methyldopa,chlortalidone, reserpine, syrosingopine, rescinnamine, prazosin,phentolamine, felodipine, propanolol, pindolol, labetalol, clonidine,captopril, enalapril, and lisonopril), beta blockers (e.g., levobunolol,pindolol, timolol maleate, bisoprolol, carvedilol, and butoxamine),alpha blockers (e.g., doxazosin, prazosin, phenoxybenzamine,phentolamine, tamsulosin, alfuzosin, and terazosin), calcium channelblockers (e.g., amlodipine, felodipine, nicardipine, nifedipine,nimodipine, nisoldipine, nitrendipine, lacidipine, lercanidipine,verapamil, gallopamil, and diltiazem), and anticlot agents (e.g.,dipyrimadole).

A variety of commonly used excipients in pharmaceutical and nutritiveformulations may be utilized with any such agents described above.Non-limiting examples of suitable excipients include an agent selectedfrom the group consisting of non-effervescent disintegrants, a coloringagent, a flavor-modifying agent, an oral dispersing agent, a stabilizer,a preservative, a diluent, a compaction agent, a lubricant, a filler, abinder, taste masking agents, an effervescent disintegration agent, andcombinations of any of these agents.

(V) Polymers

Another aspect of the present invention encompasses polymers comprisinga repeat unit having Formula (XX):

wherein,

-   -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1.

The repeat unit of the polymers disclosed herein, therefore, derivesfrom the cyclic dimer compounds of Formulas (II) or (V). In variousembodiments, R², R⁴, R⁵, R⁶, R⁷, Z, and n may vary as detailed above insection (I). For example, R², R⁴, R⁵, R⁶, and R⁷, when present, may beindependently chosen from hydrogen, alkyl, aryl, alkylaryl, substitutedalkyl, substituted aryl, and substituted alkylaryl.

In some embodiments, R¹ comprises (CR⁸R⁹)_(m)YR¹⁰R¹¹ and the repeat unitof the polymer comprises Formula (XXa):

wherein:

-   -   R², R³, R⁴, R⁵, R⁶, R⁸, R⁹, and R¹⁰ are independently chosen        from hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   R⁷ and R¹¹ are optionally present, when present they are        independently chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   Y and Z are independently chosen from nitrogen, sulfur, sulfone,        sulfoxide, and selenium; and    -   n and m are integers ≧1.

Each of R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, Y, Z, n and m may varyas described above in section (I). In various embodiments, R², R³, R⁴,R⁵, R⁸ and R⁹ are hydrogen, n and m independently range from 1 to 10; Zand Y are independently chosen from sulfur, sulfone, sulfoxide, andselenium. In some iterations, R⁶ and R¹⁰ are lower chain alkyl, and R⁷and R¹¹, if present, are independently hydrogen or lower chain alkyl. Inan exemplary embodiment, each of R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen,both n and m are 2, both Z and Y are sulfur, both R⁶ and R¹⁰ are methyl,and neither R⁷ nor R¹¹ are present.

In exemplary embodiments, the repeat unit comprises Formula (XXV):

wherein:

-   -   p is an integer greater than 1;    -   provided that when p is less than 4, then the polymer has a        polydispersity index of less than about 1.3.

The polymers comprising repeat units having Formulas (XX), (XXa), and(XXV) may have a variety of average molecular weights. In variousembodiments, the polymer may be an average molecular weight that rangesfrom about 200 to about 2,000 Da, from about 2,000 to about 5,000 Da,from about 5,000 to about 10,000 Da, from about 10,000 to about 30,000,from about 30,000 to about 60,000 Da, from about 60,000 to about 100,000Da, from about 100,000 to about 150,000 Da, from about 150,000 to about300,000 Da, from about 300,000 to about 600,000 Da, from about 600,000to about 1,000,000 Da, from about 1 million to about 2 million Da, fromabout 2 million to about 5 million Da, or greater than about 5 millionDa.

The polymers disclosed herein generally have a narrow molar massdistribution. The polydispersity index (PDI), which is equal to Mw/Mn,is generally less than about 1.8. In some embodiments, the PDI is lessthan about 1.7, less than about 1.6, less than about 1.5, less thanabout 1.4, less than about 1.3, less than about 1.2, or less than about1.1. In exemplary embodiments, the polymers have a PDI of less thanabout 1.3.

The polymers disclosed herein contain essentially no monomer or fractionof a monomer. The monomer may be a compound comprising Formula (II) or(V), which are detailed above in section (I). In certain embodiments,the monomer content of the homopolymer may be less than about 5%, lessthan about 4%, less than about 3%, less than about 2%, less than about1% of a monomer, or less than about 0.5%.

The polymers disclosed herein may be linear, ring, branched polymers orcopolymers (see below). Branched polymers include be, without limit,star polymers, comb polymers, brush polymers, dendrimers, dendronizedpolymers, and ladder polymers. Polymers prepared from optically puremonomers may be crystalline or semi-crystalline.

The polymers comprising repeat units having Formulas (XX), (XXa), or(XXV) may have one set of properties under one set of conditions and adifferent set of properties under different conditions. In someembodiments, the homopolymers provided herein may be stable in aqueoussolutions under approximately neutral pH. In other embodiments, thehomopolymers provided herein may hydrolyze in aqueous solutions at pHvalues of less than about 6.0, less than about 5.0, less than about 3.0,less than about 2.0, or less than about 1.0.

In general, the repeat unit of the polymers disclosed herein has atleast one chiral center. In particular, the alpha carbon adjacent to thecarbonyl unit may be chiral. Depending upon the identities of R², R³,R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, Y, and Z, the repeat unit may haveadditional chiral centers. Each chiral center may have an R or an Sconfiguration. In embodiments in which the repeat unit comprises Formula(XXVI), each repeat unit has two chiral carbons. Thus each repeat unitmay have an RR, RS, SR, or SS configuration.

(a) Homopolymers

In some embodiments, the polymer detailed above may be a homopolymer.That is, each repeat unit is identical throughout the length of thepolymer.

In some embodiments, the homopolymer comprises Formula (XXI):

wherein:

-   -   R is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium;    -   X is chosen from oxygen and nitrogen;    -   n is an integer ≧1; and    -   p is an integer greater than 1.

In various embodiments R may be hydrogen, alkyl, aryl, alkylaryl,substituted alkyl, substituted aryl, and substituted alkylaryl. In someembodiments, R is may be alkyl. In other embodiments, R may bepolyethylene oxide, polypropylene oxide, polyvinyl alcohol, or anotherpolymer. R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Z, and n may vary as describedabove in section (I).

In one embodiment, R¹ comprises (CR⁸R⁹)_(m)YR¹⁰R¹¹ and the polymercomprises repeat units comprising Formula (XXa), as detailed above.

In one exemplary embodiment, the polymer comprises Formula (XXV):

wherein:

-   -   R is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   X is chosen from oxygen and nitrogen; and    -   p is an integer greater than 1;    -   provided that when p is less than 4, then the polymer has a        polydispersity index of less than about 1.3.

In some embodiments of the polymer comprising Formula (XXVI), X isoxygen and R is C₁ to C₂₀ alkyl. In other embodiments of the polymercomprising Formula (XXVI), XR may be an amine.

(b) Copolymers

In some embodiments, the polymer detailed above may further comprise atleast one second repeat. That is, the polymer is a copolymer comprisinga first repeat unit comprising Formula (XX) and at least one secondrepeat unit.

In some iterations of this embodiment, the second repeat unit alsocomprises Formula (XX), however, the second repeat unit is substituteddifferently in at least one position than the first repeat unitcomprising Formula (XX).

In other iterations, the second repeat unit may be an acrylate, anaminoacrylate, an alkylene succinate, an alkylene oxalate, an amide, anamino acid, an anhydride, an arylate, a carbonate, a cellulose, acaprolactone, a cyanoacrylate, a cyclic ether, a dihydropyran, adioxane, a dioxanone, an ether ketone, an ethylene glycol, a fumarate,an hydroxyl alkanoate, an hydroxy ester, an imide, a ketal, a lactide,lactone, a methacrylate, a methyl olefin, an orthoester, a phosphazine,a styrene, a terephthalate, a tetrahydrofuran a trimethylene carbonate,an urethane, a vinyl acetate, a vinyl ketone, a vinyl halide, aderivative of any of the forgoing, or mixtures thereof. In certainembodiments, the second repeat unit a lactide, a lactone, a lactam, anhydroxyl alkanoate, a hydroxyl ester, a cyclic ether, a tetrahydrofuran,a dioxane, a dioxanone, and mixtures thereof. In exemplary embodiments,the second repeat unit may be chosen from lactide and ethylene oxide. Inone exemplary embodiment, the first repeat unit comprises Formula (XXVI)and the second repeat unit is lactide. In another exemplary embodiment,the first repeat unit comprises Formula (XXV) and the second repeat unitis ethylene oxide.

The weight ratio of the first repeat unit to the second repeat unit mayvary depending on the desired properties of the copolymer. In someaspects, the weight ratio of the first repeat unit comprising Formula(XX) to the second repeat unit may range from about 99.9:0.1 to about0.1:99.9. In various embodiments the weight ratio of the first repeatunit comprising Formula (XX) to the second repeat unit may be about99:1, 95:5, 90:10, 85:15, 80:20, 75:25, 70:30, 65:35, 60:40, 55:45,50:50, 45:55, 40:60, 35:65, 30:70, 25:75, 20:80, 15:85, 10:90, 5:95, or1:99 weight %. Similarly, in embodiments in which the combinationcomprises three or more repeat units, the amount of each compound canand will vary.

In various embodiments, the copolymer may be an average molecular weightthat ranges from about 200 to about 2,000 Da, from about 2,000 to about5,000 Da, from about 5,000 to about 10,000 Da, from about 10,000 toabout 30,000, from about 30,000 to about 60,000 Da, from about 60,000 toabout 100,000 Da, from about 100,000 to about 150,000 Da, from about150,000 to about 300,000 Da, from about 300,000 to about 600,000 Da,from about 600,000 to about 1,000,000 Da, from about 1 million to about2 million Da, from about 2 million to about 5 million Da, or greaterthan about 5 million Da.

The copolymers disclosed herein may be may be alternating copolymers,random copolymers, block copolymers, linear copolymers, graftcopolymers, or branched copolymers. Suitable branched copolymers includestar polymers, AB₂ star polymers, palm-tree AB_(n) polymers, H-shapedB₂AB₂ polymers, dumbbell polymers, star block AB_(n) polymers, starA_(n)B_(n) polymers, comb polymers, brush polymers, dendrimers,dendronized polymers, ladder polymers, and so forth. The copolymers maybe crystalline or semi-crystalline.

(VI) Polymerization Processes

A further aspect of the present disclosure provides processes for theformation of the polymers detailed above in section (V).

The polymers detailed in section (V) may be prepared by contacting aplurality of compounds comprising Formula (II) in the presence of acatalyst to form the homopolymer comprising the repeat unit comprisingFormula (XX). The compound comprising Formula (II) and the repeat unitcomprising Formula (XX) have the following structures:

wherein:

-   -   R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,        hydrocarbyl, and substituted hydrocarbyl;    -   R⁶ is chosen from hydrogen, hydrocarbyl, and substituted        hydrocarbyl;    -   R⁷ is optionally present, when present it is chosen from        hydrogen, hydrocarbyl, and substituted hydrocarbyl;    -   Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, and        selenium; and    -   n is an integer ≧1.

Each of R¹, R², R⁴, R⁵, R⁶, R⁷, Z, and n may be chosen as describedabove in section (I). In some embodiments, R¹ comprises(CR⁸R⁹)_(m)YR¹⁰R¹¹, wherein R⁸, R⁹, R¹⁰, R¹¹, Y and m may be chosen asdescribed in section (I).

In an exemplary embodiment, the reacting compounds comprise Formula (V)and the repeat unit of the polymers comprises Formula (XXVI):

The process comprises contacting a plurality of compounds comprisingFormula (II) or Formula (V) under the appropriate ring openingconditions to facilitate polymerization. In general, the polymerizationreaction is conducted in the presence of a catalyst. Suitable catalystsinclude, without limit, tin(II) octanoate (stannous octanoate),aluminum(III) isopropoxide, zinc(II) lactate, yttrium complexes, bis-and trisaryl tin complexes, heterobimetallic iron(II) complexes,titanium complexes with bridged-biphenolate ligands, cationic aluminumcomplexes, pyridine catalysts, and the like. In an exemplary embodiment,the catalyst may be stannous octanoate.

The amount of catalyst used in the reaction can and will vary. Ingeneral, the amount of catalyst may range from about 0.001 wt % of theamount of the compound comprising Formula (II) or Formula (V) to about 2wt % of the compound comprising Formula (II) or Formula (V). In someembodiments, the catalyst may be added in an amount below 2 wt %, below1 wt %, or below 0.1 wt %. More preferably, the catalyst may be providedin the reaction in a weight percentage of about 0.01, 0.02, 0.03, 0.04,0.05, 0.06, 0.07, 0.08, 0.09, or 0.10 mol % to the compound comprisingFormula (IIb).

The reaction may be conducted in the presence of a solvent.Alternatively the reaction may be conducted neat. In embodiments inwhich a solvent is included in the reaction mixture, the choice ofsolvent will depend upon the identity of the compounds comprisingFormula (II) or Formula (V). Examples of suitable solvents are detailedabove in section (IIa). In an exemplary embodiment, the solvent may betoluene. The amount of solvent added to the reaction mixture can andwill vary. Typically, the weight-to-weight ratio of the solvent to thecompound comprising Formula (II) or Formula (V) may range from about 1:1to about 100:1. In various embodiments, the weight-to-weight ratio ofthe solvent to the compound comprising Formula (II) or Formula (V) mayrange from about 1:1 to 5:1, from about 5:1 to about 20:1, from about20:1 to about 40:1, from about 40:1 to about 80:1, or from about 80:1 toabout 100:1.

The reaction mixture may further comprise a ring opening initiator. Theinitiator may be any compound (i.e., a small molecule or a polymer)comprising at least one hydroxyl group and/or an amine group. Suitableinitiators include water, alcohols, polyols (e.g., glycerol, sugaralcohols, etc,) polymers comprising hydroxyl groups (e.g., polyethyleneoxide, polypropylene oxide, polyvinyl alcohol), glycols, polyglycols,and primary or secondary amines of low molecular weight. In exemplaryembodiments the initiator may be water, methanol, ethanol, propanol,butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol,polyethylene oxide, polyvinyl alcohol, and the like.

The temperature of the polymerization reaction may vary. In general, thereaction is conducted at a temperature that ranges from about 100° C. toabout 200° C. In various embodiments, the temperature of the reactionmay range from about 100° C. to about 120° C., from about 120° C. toabout 140° C., from about 140° C. to about 160° C., from about 160° C.to about 200° C. In exemplary embodiments, the temperature of thereaction may be about 140° C., about 160° C., or any temperaturein-between. In general, the reaction is conducted under an inertatmosphere. For example, the reaction may be performed under nitrogen,under argon, or another inert gas.

The duration of the reaction can and will vary. In general, the durationof the reaction may range from about 1 hour to about 3 days. In variousembodiment, the duration of the reaction may range from about 1 to 5hours, from about 5 to 10 hours, from about 10 to 18 hours, from about18 to 24 hours, from about 24 to about 30 hours, from about 30 to about40 hours, or from about 40 hours to about 60 hours.

In some embodiments, the polymer may be prepared by an extrusionprocess. Generally, processes of extrusion involve feeding the reactionmixture into an extruder which heats and shears the mixture. Generally,shearing occurs through an apparatus which pushes the heated polymerthrough an orifice. The extruder may be chosen from any commerciallyavailable extruder and may be a single screw extruder or preferably atwin-screw extruder that mechanically shears the mixture with the screwelements.

In general, substantially all of the compounds comprising Formula (II)or Formula (V) are polymerized and converted into the polymer. Invarious embodiments, the conversion of the compounds comprising Formula(II) or Formula (V) may be greater than about 90%, greater than about95%, greater than about 98%, or greater than about 99%. In general, thepolymer is substantially free of monomer (i.e., the compound comprisingFormula (IIb) or Formula (V)).

The resultant polymer may be isolated and/or purified from the reactionmixture using means well known in the art including size exclusionchromatography, HPLC, ion-exchange chromatography, other types ofchromatography, precipitation, and/or crystallization.

The copolymers detailed in section (V)(b) may be prepared by contactinga plurality of compounds comprising Formula (II) or Formula (V) with aplurality of at least one additional type of monomer during thepolymerization process. The additional monomers may be addedconcurrently with the compounds comprising Formula (II) or Formula (V),may be added after the compounds comprising Formula (II) or Formula (V),or may be added alternately with the compounds comprising Formula (II)or Formula (V). Those skilled in the art will appreciate that manyvariations are possible, considering the many different types ofcopolymers that can be made.

The additional monomers may be chosen from acrylates, aminoacrylates,alkylene succinates, alkylene oxalates, amides, amino acids, anhydrides,arylates, carbonates, cellulose, caprolactone, caprolactam,cyanoacrylates, cyclic ethers, dihydropyrans, dioxanes, dioxanones,ether ketones, ethylene glycol, fumarates, hydroxy alkanoates, hydroxyesters, imides, ketals, lactides, lactones, methacrylates, methylolefins, orthoesters, phosphazines, styrenes, terephthalates,tetrafurans. trimethylene carbonate, urethanes, vinyl acetates, vinylketones, vinyl halides, derivatives, isomers, and mixtures thereof.

The ratio of the additional monomer to the compounds comprising Formula(II) or Formula (V) may range from about 99.9:0.1 to about 0.1:99.9weight %. For example, additional monomers may be provided in a ratio of99:1, 95:5, 90:10, 85:15, 80:20, 75:25, 70:30, 65:35, 60:40, 55:45,50:50, 45:55, 40:60, 35:65, 30:70, 25:75, 20:80, 15:85, 10:90, 5:95, or1:99 weight % to the compounds comprising Formula (II) or Formula (V).Similarly, in embodiments in which the combination comprises three ormore monomers, the amount of each monomer can and will vary.

(VII) Applications

The polymers detailed above in section (V) may be used in a variety ofapplications. Non-limiting examples of suitable uses includeplasticizers, processing aids, adhesives, coatings, lacquers, films,emulsifiers, antioxidant agents, antimicrobial agents, anticorrosiveagents, nutritive agents, or feed additives. In various embodiments, thepolymers disclosed herein may be used in packaging materials (e.g.,trash bags, biodegradable bags, grocery bags, wrappings, foodcontainers, film wrapping, laminated papers, bottles), consumer goods(e.g., fast-food tableware, containers, egg cartons, razor handles,toothbrushes, pens, cartridges, toys), disposable non-wovens (e.g.,engineered fabrics; diaper backings, surgical gowns, drapes, and thelike), cosmetics, personal care products, home care products, medicalapplications (e.g., drug delivery, scaffolds for tissue engineering,medical prostheses, wound dressing, sutures, bone replacement, fixationof fractures, fixation of ligaments, cartilage repair, menisci repair,medical devices, stents, orthopedic/surgical materials (e.g., screws,pins, plugs, etc.), haemostatic devices, sensor devices), andagricultural applications (e.g., mulch films, planters).

(VIII) Polymer Compositions

In yet another aspect, the present disclosure encompasses polymercompositions. In some embodiments, the polymer composition comprises afirst polymer as described in section (V) and at least one additionalpolymer to form a polymer blend. As used herein, a blend is amacroscopic homogeneous or miscible mixture of two or more differentpolymers and is formed by tailoring compositions to meet specificend-use requirements.

In various embodiments, the additional polymer may be selected fromcrystalline and semicrystalline polymers. Examples of suitable polymers,without limitation, are polymers of acrylates, aminoacrylates, alkylenesuccinates, alkylene oxalates, amides, amino acids, anhydrides,arylates, carbonates, cellulose, caprolactone, cyanoacrylates, cyclicethers, dihydropyrans, dioxanes, dioxanones, ether ether ketones,ethylene glycol, fumarates, hydroxy alkanoates, hydroxy esters, imides,ketals, lactides, lactones, methacrylates, methyl olefins, orthoesters,phosphazines, styrenes, terephthalates, tetrafurans. trimethylenecarbonate, urethanes, vinyl acetates, vinyl ketones, vinyl halides,derivatives, isomers, and mixtures thereof. In exemplary embodiments,the second polymer may be chosen from poly(lactide), poly(ethylcellulose), and polyvinyl alcohol.

The additional polymer may vary in molecular weight. In someembodiments, the additional polymer may range from about 500 Da togreater than 1,000,000 Da. In some embodiments, the molecular weight ofthe additional polymer may be about 2,000 Da, 10,000 Da, 20,000 Da,30,000 Da, 40,000 Da, 50,000 Da, 60,000 Da, 70,000 Da, 80,000 Da, 90,000Da, 100,000 Da, 500,000 Da, 1,000,000 Da and may range between andincluding any two of these values. The additional polymer may becharacterized by a weight-average molecular weight. In some aspects, theweight-average molecular weight of the additional polymer used in theblend may be at least 500 Da. In other aspects, the weight-averagemolecular weight of the additional polymers may be about 1,000 Da toabout 1,000,000 Da.

The amount of the first polymer detailed in section (V) and theadditional polymer may depend on the desired properties of thecombination. In some aspects, the weight ratio of the first polymer tothe additional polymer may range from about 99.9:0.1 to about 0.1:99.9weight %. In various embodiments the weight ratio of the first polymerto the additional polymer may be about 99:1, 95:5, 90:10, 85:15, 80:20,75:25, 70:30, 65:35, 60:40, 55:45, 50:50, 45:55, 40:60, 35:65, 30:70,25:75, 20:80, 15:85, 10:90, 5:95, or 1:99 weight %. In some embodiments,the blend comprises more than one additional polymer. In embodiments inwhich the combination comprises two or more additional polymers, theamount of each polymer can and will vary.

In other embodiments, the polymer composition may be a feed compositioncomprising a polymer from section (V) and at least one additional agentchosen from one or more of the following: carbohydrates, fats, proteins,amino acids, and alpha hydroxy acids. Suitable sources of carbohydratesfats, proteins, amino acids, and alpha hydroxy acids are detailed abovein section (IV)(a). In still other embodiments, the polymer compositionmay comprise a polymer from section (V) and at least one nutritiveand/or pharmaceutical agent. Suitable nutritive and pharmaceuticalagents are detailed above in section (IV)(b).

DEFINITIONS

When introducing elements of the embodiments described herein, thearticles “a”, “an”, “the” and “said” are intended to mean that there areone or more of the elements. The terms “comprising”, “including” and“having” are intended to be inclusive and mean that there may beadditional elements other than the listed elements.

The compounds described herein have asymmetric centers. Compounds of thepresent invention containing an asymmetrically substituted atom may beisolated in optically active or racemic form. All chiral,diastereomeric, racemic forms and all geometric isomeric forms of astructure are intended, unless the specific stereochemistry or isomericform is specifically indicated.

The term “acyl,” as used herein alone or as part of another group,denotes the moiety formed by removal of the hydroxyl group from thegroup COON of an organic carboxylic acid, e.g., RC(O)—, wherein R is R¹,R¹O—, R¹R²N—, or R¹S—, R¹ is hydrocarbyl, heterosubstituted hydrocarbyl,or heterocyclo, and R² is hydrogen, hydrocarbyl, or substitutedhydrocarbyl.

The term “acyloxy,” as used herein alone or as part of another group,denotes an acyl group as described above bonded through an oxygenlinkage (O), e.g., RC(O)O— wherein R is as defined in connection withthe term “acyl.”

The term “allyl,” as used herein not only refers to compound containingthe simple allyl group (CH₂═CH—CH₂—), but also to compounds that containsubstituted allyl groups or allyl groups forming part of a ring system.

The term “alkyl” as used herein describes groups which are preferablylower alkyl containing from one to eight carbon atoms in the principalchain and up to 20 carbon atoms. They may be straight or branched chainor cyclic and include methyl, ethyl, propyl, isopropyl, butyl, hexyl andthe like.

The term “alkenyl” as used herein describes groups which are preferablylower alkenyl containing from two to eight carbon atoms in the principalchain and up to 20 carbon atoms. They may be straight or branched chainor cyclic and include ethenyl, propenyl, isopropenyl, butenyl,isobutenyl, hexenyl, and the like.

The term “alkoxide” or “alkoxy” as used herein is the conjugate base ofan alcohol. The alcohol may be straight chain, branched, cyclic, andincludes aryloxy compounds.

The term “alkynyl” as used herein describes groups which are preferablylower alkynyl containing from two to eight carbon atoms in the principalchain and up to 20 carbon atoms. They may be straight or branched chainand include ethynyl, propynyl, butynyl, isobutynyl, hexynyl, and thelike.

The term “aromatic” as used herein alone or as part of another groupdenotes optionally substituted homo- or heterocyclic conjugated planarring or ring system comprising delocalized electrons. These aromaticgroups are preferably monocyclic (e.g., furan or benzene), bicyclic, ortricyclic groups containing from 5 to 14 atoms in the ring portion. Theterm “aromatic” encompasses “aryl” groups defined below.

The terms “aryl” or “Ar” as used herein alone or as part of anothergroup denote optionally substituted homocyclic aromatic groups,preferably monocyclic or bicyclic groups containing from 6 to 10 carbonsin the ring portion, such as phenyl, biphenyl, naphthyl, substitutedphenyl, substituted biphenyl, or substituted naphthyl.

The term “copolymer” refers to a polymer containing two or moredifferent repeat units.

The term “crystalline polymer” as used herein refers to a polymer havingthe characteristic or regular three-dimensional packing.

The term “enrichment” means an amount above the statistical distributionif all chiral centers had an equal probability of being alpha or beta.

The terms “carbocyclo” or “carbocyclic” as used herein alone or as partof another group denote optionally substituted, aromatic ornon-aromatic, homocyclic ring or ring system in which all of the atomsin the ring are carbon, with preferably 5 or 6 carbon atoms in eachring. Exemplary substituents include one or more of the followinggroups: hydrocarbyl, substituted hydrocarbyl, alkyl, alkoxy, acyl,acyloxy, alkenyl, alkenoxy, aryl, aryloxy, amino, amido, acetal,carbamyl, carbocyclo, cyano, ester, ether, halogen, heterocyclo,hydroxyl, keto, ketal, phospho, nitro, and thio.

The terms “epoxy” or “epoxide” as used herein means a cyclic ether. Thering structure generally comprises from 2 to 5 carbon atoms in the ring.

The terms “halogen” or “halo” as used herein alone or as part of anothergroup refer to chlorine, bromine, fluorine, and iodine.

The term “heteroatom” refers to atoms other than carbon and hydrogen.

The term “heteroaromatic” as used herein alone or as part of anothergroup denotes optionally substituted aromatic groups having at least oneheteroatom in at least one ring, and preferably 5 or 6 atoms in eachring. The heteroaromatic group preferably has 1 or 2 oxygen atoms and/or1 to 4 nitrogen atoms in the ring, and is bonded to the remainder of themolecule through a carbon. Exemplary groups include furyl, benzofuryl,oxazolyl, isoxazolyl, oxadiazolyl, benzoxazolyl, benzoxadiazolyl,pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl,pyrimidyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl, indolizinyl,benzimidazolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl,carbazolyl, purinyl, quinolinyl, isoquinolinyl, imidazopyridyl, and thelike. Exemplary substituents include one or more of the followinggroups: hydrocarbyl, substituted hydrocarbyl, alkyl, alkoxy, acyl,acyloxy, alkenyl, alkenoxy, aryl, aryloxy, amino, amido, acetal,carbamyl, carbocyclo, cyano, ester, ether, halogen, heterocyclo,hydroxyl, keto, ketal, phospho, nitro, and thio.

The terms “heterocyclo” or “heterocyclic” as used herein alone or aspart of another group denote optionally substituted, fully saturated orunsaturated, monocyclic or bicyclic, aromatic or non-aromatic groupshaving at least one heteroatom in at least one ring, and preferably 5 or6 atoms in each ring. The heterocyclo group preferably has 1 or 2 oxygenatoms and/or 1 to 4 nitrogen atoms in the ring, and is bonded to theremainder of the molecule through a carbon or heteroatom. Exemplaryheterocyclo groups include heteroaromatics as described above. Exemplarysubstituents include one or more of the following groups: hydrocarbyl,substituted hydrocarbyl, alkyl, alkoxy, acyl, acyloxy, alkenyl,alkenoxy, aryl, aryloxy, amino, amido, acetal, carbamyl, carbocyclo,cyano, ester, ether, halogen, heterocyclo, hydroxyl, keto, ketal,phospho, nitro, and thio.

The term “homopolymer” refers to a polymer containing a single type ofrepeat unit.

The terms “hydrocarbon” and “hydrocarbyl” as used herein describeorganic compounds or radicals consisting exclusively of the elementscarbon and hydrogen. These moieties include alkyl, alkenyl, alkynyl, andaryl moieties. These moieties also include alkyl, alkenyl, alkynyl, andaryl moieties substituted with other aliphatic or cyclic hydrocarbongroups, such as alkaryl, alkenaryl and alkynaryl. Unless otherwiseindicated, these moieties preferably comprise 1 to 20 carbon atoms.

The term “protecting group” as used herein denotes a group capable ofprotecting a particular moiety, wherein the protecting group may beremoved, subsequent to the reaction for which the protection isemployed, without disturbing the remainder of the molecule. A variety ofprotecting groups and the synthesis thereof may be found in “ProtectiveGroups in Organic Synthesis” by T. W. Greene and P. G. M. Wuts, JohnWiley & Sons, 1999.

The term “semi-crystalline polymer” as used herein refers to a polymerwith both regions that are “crystalline” as describe above, and regionsthat are amorphous, having no regular packing to the three-dimensionalstructure.

The “substituted hydrocarbyl” moieties described herein are hydrocarbylmoieties which are substituted with at least one atom other than carbon,including moieties in which a carbon chain atom is substituted with aheteroatom such as nitrogen, oxygen, silicon, phosphorous, boron, or ahalogen atom, and moieties in which the carbon chain comprisesadditional substituents. These substituents include alkyl, alkoxy, acyl,acyloxy, alkenyl, alkenoxy, aryl, aryloxy, amino, amido, acetal,carbamyl, carbocyclo, cyano, ester, ether, halogen, heterocyclo,hydroxyl, keto, ketal, phospho, nitro, and thio.

Having described the invention in detail, it will be apparent thatmodifications and variations are possible without departing from thescope of the invention defined in the appended claims.

EXAMPLES

The following examples illustrate various embodiments of the invention.

Example 1 Preparation of 3,6-bis(2-Methylthio)ethyl-1,4-dioxane-2,5Dione

The cyclic dimer 3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione wasprepared according to the following reaction scheme:

A solution of 524.6 g of Alimet® (88% 2-hydroxy-4-(methylthio)butanoicacid (HMTBa) in toluene (14054 g) was treated with catalytic p-toluenesulfonic acid monohydrate (21.1 g). The reaction flask was fitted with aDean Stark trap and condenser. The reaction was heated to 110° C. andapproximately 95 mL of water was collected over about 5 hours. After 5hours, the reaction was cooled to room temperature and washed twice withsaturated sodium bicarbonate, and twice with water. The toluene was thenremoved under reduced pressure. The residue was dried to a solid underhigh vacuum. To the solid residue was then added 300 mL of methylt-butyl ether, and the solid dissolved at 50° C. The solution was cooledto ambient temperature, and then to 2-4° C. to crystallize. The solutionwas warmed to ambient temperature and the solid filtered off and washedwith minimal methyl t-butyl ether. The solid was dried on high vacuum togive 91.4 g (22 mol) of an off-white solid. LC/MS showed a racemicmixture (2 peaks) both with M+H=265, M+Na=287. ¹H NMR (500 MHz,CHLOROFORM-d, racemic mixture) ppm 2.07-2.16 (m, 6H), 2.21-2.46 (m, 4H),2.65-2.83 (m, 4H), 5.17-5.32 (m, 2H). TLC (25% ethyl acetate/heptanes)rf: 0.16.

Example 2 Distillation of 2-Hydroxy-4-(Methylthio)butanoic Acid

In a flask 11 g of HMTBa and 11 mL of conc. HCl were added. The mixturewas heated to 90° C. for 1 hour. The mixture was cooled and thenconcentrated at 5-10 Torr for 1.25 hrs until the pot temperature reached100° C. After cooling to room temperature an aliquot of the reactionmixture was analyzed by HPLC. The chromatogram shown in FIG. 1A revealsthe presence of monomers, dimers, trimers, and tetramers of HMTBa in thereaction mixture. To confirm that no cyclic dimer was present in thereaction mixture, an aliquot of the cyclic dimer prepared essentially asdescribed in Example 1 was subjected to HPLC (using the same parametersas used for the analysis of the reaction mixture). FIG. 1B presents anoverlay of the cyclic dimer chromatogram onto the HMTBa oligomerchromatogram. This analysis revealed that the cyclic dimer had adifferent elution time than the HMTBa oligomers.

Example 3 Azeotropic Distillation of 2-Hydroxy-4-(Methylthio)butanoicAcid

In a flask was added purified HMTBa and xylenes (no acid was present).The mixture was heated and water was removed by azetropic distillationfor 4-6 hours. After cooling to room temperature an aliquot of thereaction mixture was analyzed by HPLC. As shown in FIG. 2A, the samplecontained monomers, dimers, trimers, and tetramers of HMTBa, but nocyclic dimer. To confirm this, an aliquot of the cyclic dimer preparedessentially as described in Example 1 was subjected to HPLC (using thesame parameters as used for the analysis of the reaction mixture). FIG.2B presents an overlay of the cyclic dimer chromatogram onto the HMTBaoligomer chromatogram. This analysis revealed that the cyclic dimer hada different elution time than the HMTBa oligomers.

Example 4 Separation of Diastereomers

Alimet® and p-toluene sulfonic acid were reacted as described inExample 1. An aliquot (4.7 g) of the resulting solid was subjected tochiral chromatography (Chiralpak IA column, eluted with 70:30 hexane:THFat 25° C., with UV detection at 220 nm) and yielded three samples of thedifferent diastereomers. The samples are detailed in Table 6.

TABLE 6 Diastereomer Samples Sample Diastereomer Excess Retention timeRecovery* #1 >99% 5.323 min 1.09 g (92.9%) #2 99.3%  6.464 min 1.18 g(100%) #3 >99% 12.295 min  2.09 g (89.3%) *% recovery does not take intoaccount any residual BHT left in the product

(−)-3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione

315 mg of #1 was suspended in 10 mL of methyl t-butyl ether and thenfiltered, and dried under high vacuum to give 235 mg of #1 with 98.7%purity (HPLC). α_(D) ²⁵ (c=1.042, CH₂Cl₂): −250.212. LCMS MH+ 265, M+Na287.

(+)-3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione

309 mg of #2 was suspended in 10 mL of methyl t-butyl ether and thenfiltered, and dried under high vacuum to give 190 mg of #2 with >99%purity (HPLC). α_(D) ²⁵ (c=1.037, CH₂Cl₂): +250.263. LCMS MH+ 265, M+Na287.

(meso)-3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione

420 mg of #3 was suspended in 10 mL of methyl t-butyl ether and thenfiltered, and dried under high vacuum to give 250 mg of #3 with 96%purity (HPLC). α_(D) ²⁵ (c=1.036, CH₂Cl₂):=0° (racemic). LCMS MH+ 265,M+Na 287.

Example 5 Polymerization of 3,6-bis(2-Methylthio)ethyl-1,4-dioxane-2,5Dione

Into a 25 ml flask was placed 1.5 grams of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione as prepared in Example1 and a stirring bar, and then vacuum was applied on this flask for 1.5h. Then 0.15 ml of catalyst solution (stannous octoate in toluene, 7.63mM) was injected into the flask, which was filled with nitrogen. Thetemperature of the mixture was controlled at 140° C. for 48 hours.Analysis of the polymer by gel permeation chromatography (GPC) revealedthat the number-average molar mass (Mn) was 3470 g/mol.(Mn=Σn_(i)/Σn_(i)/M_(i)). The Polydispersity Index (PDI) was 1.26.(PDI=Mw/Mn; Mw=mass-average molar mass=Σn_(i)M_(i)/Σn_(i)).

Example 6 Polymerization-Trial 2

Into a 25 ml flask was placed 1.5 grams of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione and a stirring bar, andthen a vacuum was applied on this flask for 1.5 h. Then 0.15 ml ofcatalyst solution (stannous octoate in toluene, 7.63 mM) was injectedinto the flask, which was filled with nitrogen, followed by addition of2.5 mg of 1-octanol. The temperature of the mixture was controlled at140° C. for 48 hours. Analysis of the resultant polymer revealed that ithad a Mn of 2620 g/mol and a PDI of 1.5.

Example 7 Polymerization-Trial 3

Into a 25 ml flask was placed a magnetic stirring bar and 1.5 grams of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione which was dried invacuum oven at 30° C. for 3 days. The monomer was further dried on avacuum line at room temperature. After the flask was filled with dry N₂,0.15 ml of catalyst (stannous octoate in toluene, 7.63 mM) was added.The temperature of the polymerization was controlled at 160° C. for 48hours. Analysis of the polymer revealed that the Mn was 4700 g/mol andthe PDI was 1.46.

Example 8 Polymerization-Trial 4

Into a 25 ml flask was placed a magnetic stirring bar and 1.5 grams of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione which was dried invacuum oven at 30° C. for 3 days. The monomer was further dried on avacuum line at room temperature. After the flask was filled with dry N₂,0.15 ml of catalyst (stannous octoate in toluene, 7.63 mM) and 3.25 mgoctanol was added. The temperature of the polymerization was controlledat 160° C. for 48 hours. GPC analysis revealed that the polymer had a Mnof 3500 g/mol and a PDI of 1.69.

Example 9 Polymerization-Trial 5

Into a 25 ml flask was placed a magnetic stirring bar and 1.5 grams of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione which was dried invacuum oven at 50° C. overnight. The monomer was further dried on avacuum line at room temperature for 1 hour. After the flask was filledwith dry N₂, 4.5 mg of stannous octoate was added. The temperature ofthe polymerization was ramped to and controlled at 140° C. for 28 hours.Analysis revealed that the Mn of the polymer was 8600 g/mol and the PDIwas 1.27. The structure of the polymer was analyzed by ¹H-NMR. FIG. 3presents the NMR spectrum.

Example 10 Polymerization-Trial 6

Into a 25 ml flask was placed a magnetic stirring bar and 1.5 grams of3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione which was dried byvacuum pumping at 50° C. for several days. The monomer was further driedon a vacuum line at room temperature for 1 hour. After the flask wasfilled with dry N₂, 3 mg of stannous octoate was added. The temperatureof the polymerization was ramped to and controlled at 140° C. for 22hours. GPC analysis revealed that the Mn of the polymer was 3.3×10⁴g/mol and the PDI was 1.22. GPC coupled with light scattering detectors(GPC-LS) revealed that the Mn was 8.8×10⁴ g/mol and the PDI was of 1.34.

Example 11 Polymerization-Trial 7

Into a 25 ml shlenk reaction tube was placed a magnetic stirring bar and10.24 grams of 3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione whichwas thoroughly dried by vacuum at 50° C. for several days. The monomerwas further dried on a vacuum line at 58° C. for 2 hour. After thereactor was filled with dry N₂, 9 mg of stannous octoate was added. Thetemperature of the polymerization was ramped to and controlled at 140°C. for 21 hours. GPC analysis revealed an Mn of 6.3×10⁴ g/mol and a PDIwas 1.52. GPC-LS analysis revealed that the Mn was 1.1×10⁵ g/mol and thePDI was 1.36.

Example 12 Polymerization-Trial 8

Into a 500 ml shlenk reaction flask was placed 120 grams of dry3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione, which was furtherdried on a vacuum line for 2.5 hours at 60° C. After the flask wasfilled with dry N₂, 0.1 ml of stannous octoate and 19 ml of octanol wereinjected to initiate the ring opening polymerization of the monomer. Themixture was heated up to and thermostated at 140° C. The reaction wascontinued for 2.5 hours. The polymer was recovered by pouring thereaction mixture into a container under N₂ protection. Conversion of themonomer was 98%. GPC analysis revealed that the Mn of the polymer was1.3×10³ g/mol and the PDI was 1.2.

Example 13 Kinetic Study of Ring Opening Polymerization

Into a 500 ml shlenk reaction flask was placed 122 grams of dry3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione, which was furtherdried on a vacuum line for 1 hour at 53-60° C. After the flask wasfilled with dry N₂, 0.1 ml of stannous octoate was injected to catalyzethe ring opening polymerization of the monomer. The mixture was heatedup to and thermostated at 140° C. The reaction was continued for 23.5hours. At certain interval of reaction time, aliquots were removed andthe molecular weight was analyzed by GPC. The GPC chromatograms from thevarious time points are shown in FIG. 4. The final polymer was recoveredby pouring the reaction mixture into a container under N₂ protection.Conversion of the monomer was 96.1%. The Mn of the polymer was 4.35×10⁴g/mol and the PDI was 1.58.

Example 14 Depolymerization of Polymer Formed From3,6-bis(2-Methylthio)ethyl-1,4-dioxane-2,5 Dione

First, the polymer was formed by charging 3.5 g of the cyclic dimer(3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione) into a shlenkreaction flask, followed by injection of 0.15 ml of octanol and 5droplets of stannous octoate (−15 mg). The reaction mixture was heatedup to 140° C. and the reaction was allowed to proceed for 24 hours. Analiquot of the mixture was sampled and the conversion of the cyclicdimer to the polymer was determined to be 95 wt % (the concentration ofcyclic dimer in the final mixture was 5%) (see FIG. 5).

For the thermal cracking step, the reactor was set up with distillationapparatus. The temperature of the mixture was raised to 200° C. andvacuum (˜500 mTorr) was applied. The distillation was continued for 2hours. An aliquot of the distilled reaction mixture and the distillateswere analyzed by HPLC (see FIG. 6 and FIG. 7, respectively). Both HMTBaand the cyclic dimer (3,6-bis(2-methylthio)ethyl-1,4-dioxane-2,5 dione)were detected in the distillates. The mixture in the reaction pot wasanalyzed by GPC and it was determined that the concentration of cyclicdimer was 8.8%. The increase of the concentration of the cyclic dimerand the presence of HMTBA in the distillate strongly suggests thedecomposition of the polymer into monomers during the thermal crackingstep.

Example 15 Depolymerization of Polymer

The polymer was formed by charging 3.0 g of cyclic dimer into a shlenkreaction flask, followed by injection of 5 droplets of stannous octoate(−15 mg). The reaction mixture was heated to 140° C. and reacted for 22hours. An aliquot of the mixture was sampled and the conversion of thecyclic dimer to the polymer was determined to be 97%.

For the thermal cracking step, the reactor was set up with a condenserand connected to a vacuum (200-500 mTorr). The temperature of themixture was raised to 200° C. and kept for 2.5 h. The final reactionmixture was analyzed by GPC, which revealed that the concentration ofthe cyclic dimer in the mixture was 7.0%.

Example 16 Depolymerization of Polymer Formed from HMTBa

To a flask was added 4.0 g of oligomers of HMTBa (Mn=1.0×10³ g/mol) madeby polycondensation and the oligomers were dried in a vacuum at 60° C.overnight. The oligomers were heated (further polymerized) at 140° C.for 1 hour. After that, the flask was cooled down and about 15 mg of tincatalyst was added. The flask was transferred to Kugelrohr fordepolymerization of the oligomer at 200° C. for 2 hours and under avacuum (500 mTorr˜1 Torr). The distillates were collected. Both of thedistillates and the mixture in the flask were analyzed by HPLC and GPC.The distillates had cyclic dimers with 90.7% purity by HPLC, yield 0.62grams. The cyclic dimer concentration in the reaction mixture was 4.3%.An estimation of cyclic dimer yield in this reaction was 18%. An HPLCspectrum of the distillates is shown in FIG. 8.

What is claimed is:
 1. A compound comprising Formula (I):

wherein: X¹ and X² are chosen from nitrogen and oxygen, provided thatboth X¹ and X² are not nitrogen; R¹, R², R³, R⁴, and R⁵ areindependently chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁶ is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁷ is optionally present, when present it is chosen fromhydrogen, hydrocarbyl, and substituted hydrocarbyl; Z is chosen fromnitrogen, sulfur, sulfone, sulfoxide, and selenium; and n is an integer≧1; provided that when Z is sulfur and n is 1, then R¹ and R³ are otherthan hydrogen; and when Z is nitrogen, n is from 2 to 4, and R³ ishydrogen, then R¹ is other than hydrogen or methyl.
 2. The compound ofclaim 1, wherein R¹, R², R³, R⁴, and R⁵ are hydrogen; n is from 1 to 10;Z is chosen from sulfur, sulfone, sulfoxide, and selenium; R⁶ is lowerchain alkyl, and R⁷, if present, is hydrogen or lower chain alkyl. 3.The compound of claim 1, wherein the compound comprises Formula (Ia):

wherein: X¹ and X² are chosen from nitrogen and oxygen, provided thatboth X¹ and X² are not nitrogen; R², R³, R⁴, R⁵, R⁶, R⁸, R⁹, and R¹⁰ areindependently chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁷ and R¹¹ are optionally present, when present they areindependently chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; Y and Z are independently chosen from nitrogen, sulfur,sulfone, sulfoxide, and selenium; and n and m are integers ≧1.
 4. Thecompound of claim 3, wherein R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen;each of n and m is from 1 to 10; Y and Z are independently chosen fromsulfur, sulfone, sulfoxide, and selenium; R⁶ and R¹⁰ are lower chainalkyl; and R⁷ and R¹¹, if present, are independently hydrogen or lowerchain alkyl.
 5. The compound of claim 1, wherein the compound comprisesFormula (II):

wherein: R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,hydrocarbyl and substituted hydrocarbyl; R⁶ is chosen from hydrogen,hydrocarbyl, and substituted hydrocarbyl; R⁷ is optionally present, whenpresent it is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n is an integer ≧1; provided that when Z is sulfur and nis 1, then R¹ and R³ are other than hydrogen; and when Z is nitrogen, nis 2 or 4, and R³ is hydrogen, then R¹ is other than methyl.
 6. Thecompound of claim 5, wherein R¹, R², R³, R⁴, and R⁵ are hydrogen; n isfrom 1 to 10; Z is chosen from sulfur, sulfone, sulfoxide, and selenium;R⁶ is lower chain alkyl, and R⁷, if present, is hydrogen or lower chainalkyl.
 7. The compound of claim 5, wherein the compound comprisesFormula (IIb):

wherein: R¹ is chosen from hydrogen, alkyl, aryl, alkylaryl, substitutedalkyl, substituted aryl, and substituted alkylaryl; and R⁶ is chosenfrom hydrogen, alkyl, aryl, alkylaryl, substituted alkyl, substitutedaryl, and substituted alkylaryl.
 8. The compound of claim 5, wherein thecompound comprises Formula (IIc):


9. The compound of claim 5, wherein the compound comprises Formula(IIa):

wherein: R², R³, R⁴, R⁵, R⁶, R⁸, R⁹, and R¹⁰ are independently chosenfrom hydrogen, hydrocarbyl, and substituted hydrocarbyl; R⁷ and R¹¹ areoptionally present, when present they are independently chosen fromhydrogen, hydrocarbyl, and substituted hydrocarbyl; Y and Z areindependently chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n and m are integers ≧1.
 10. The compound of claim 9,wherein R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen; each of n and m is from1 to 10; Y and Z are independently chosen from sulfur, sulfone,sulfoxide, and selenium; R⁶ and R¹⁰ are lower chain alkyl; and R⁷ andR¹¹, if present, are independently hydrogen or lower chain alkyl. 11.The compound of claim 9, wherein the compound comprises Formula (V):


12. The compound of claim 11, wherein the compound comprises a racemicmixture.
 13. The compound of claim 11, wherein ring atoms 3 and 6 havean L configuration.
 14. The compound of claim 11, wherein ring atoms 3and 6 have an D configuration.
 15. The compound of claim 11, whereinring atoms 3 and 6 have a meso configuration.
 16. The compound of claim1, wherein the compound comprises Formula (III):

wherein: R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,hydrocarbyl and substituted hydrocarbyl; R⁶ is chosen from hydrogen,hydrocarbyl, and substituted hydrocarbyl; R⁷ is optionally present, whenpresent it is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n is an integer to ≧1.
 17. The compound of claim 16,wherein R¹, R², R³, R⁴, and R⁵ are hydrogen; n is from 1 to 10; Z ischosen from sulfur, sulfone, sulfoxide, and selenium; R⁶ is lower chainalkyl, and R⁷, if present, is hydrogen or lower chain alkyl.
 18. Thecompound of claim 16, wherein the compound comprises Formula (IIIa):

wherein: R², R³, R⁴, R⁵, R⁶, R⁸, R⁹, and R¹⁰ are independently chosenfrom hydrogen, hydrocarbyl, and substituted hydrocarbyl; R⁷ and R¹¹ areoptionally present, when present they are independently chosen fromhydrogen, hydrocarbyl, and substituted hydrocarbyl; Y and Z areindependently chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n and m are integers ≧1.
 19. The compound of claim 18,wherein R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen; each of n and m is from1 to 10; Y and Z are independently chosen from sulfur, sulfone,sulfoxide, and selenium; R⁶ and R¹⁰ are lower chain alkyl; and R⁷ andR¹¹, if present, are independently hydrogen or lower chain alkyl. 20.The compound of claim 1, wherein ring atoms 3 and 6 have a configurationchosen from RR, RS, SR, and SS, respectively.
 21. The compound of claim1, wherein the compound comprises a mixture of at least two differentisomers, each isomer having a configuration at ring atoms 3 and 6 chosenfrom RR, RS, SR, and SS, respectively.
 22. The compound of claim 1,wherein the compound hydrolyzes in an aqueous solution at a pH belowabout 5.0.
 23. The compound of claim 1, wherein the compound is used asa nutritive agent, a feed composition, or a feed premix.
 24. A feedcomposition comprising the compound of claim 1, a carbohydrate source, aprotein source, and a fat source.
 25. A composition comprising thecompound of claim 1 and at least one nutritive and/or pharmaceuticalagent.
 26. A process for preparing a compound comprising Formula (IX),the process comprising (a) contacting a compound comprising Formula (VI)with a compound comprising Formula (VII) or a compound comprisingFormula (VIII) and an acid catalyst and (b) dehydrating the resultingreaction mixture to form the compound comprising Formula (IX), thecompounds comprising Formula (IX), (VI), (VII), and (VIII):

wherein: X¹ is chosen from oxygen and nitrogen, R¹, R², R³, R⁴, and R⁵are independently chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁶ is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁷ is optionally present, when present it is chosen fromhydrogen, hydrocarbyl, and substituted hydrocarbyl; Z is chosen fromnitrogen, sulfur, sulfone, sulfoxide, and selenium; and n is an integer≧1.
 27. The process of claim 26, wherein the acid catalyst is p-toluenesulfonic acid; the reaction mixture is heated to a temperature fromabout 100° C. to about 150° C.; and the reaction mixture is dehydratedby distillation.
 28. The process of claim 26, wherein the compoundcomprising Formula (VI) and the compound comprising Formula (VIII) bothcomprise Formula (VIb) and the compound comprising Formula (IX)comprises Formula (V):


29. The process of claim 26, wherein the compound comprising Formula(IX) is isolated as a substantially pure isomer, the isomer having aconfiguration at ring atoms 3 and 6 chosen from RR, RS, SR, and SS,respectively.
 30. A process for preparing a compound comprising Formula(IX), the process comprising (a) heating a compound comprising Formula(VI) with a compound comprising Formula (VII) or a compound comprisingFormula (VIII) to form a polymer and (b) heating the polymer at atemperature of about 200° C. and a pressure of less than about 1 Torr toform the compound comprising Formula (IX), the compounds comprisingFormula (IX), (VI), (VII), and (VIII):

wherein: X¹ is chosen from oxygen and nitrogen, R¹, R², R³, R⁴, and R⁵are independently chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁶ is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; R⁷ is optionally present, when present it is chosen fromhydrogen, hydrocarbyl, and substituted hydrocarbyl; Z is chosen fromnitrogen, sulfur, sulfone, sulfoxide, and selenium; and n is an integer≧1.
 31. The process of claim 30, wherein the compound comprising Formula(VI) and the compound comprising Formula (VIII) both comprise Formula(VIb) and the compound comprising Formula (IX) comprises Formula (V):


32. The process of claim 30, wherein step (a) is conducted at atemperature from about 100° C. to about 150° C.
 33. The process of claim30, wherein the compound comprising Formula (IX) is isolated as asubstantially pure isomer, the isomer having a configuration at ringatoms 3 and 6 chosen from RR, RS, SR, and SS, respectively.
 34. Apolymer comprising a repeat unit comprising Formula (XX):

wherein: R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,hydrocarbyl, and substituted hydrocarbyl; R⁶ is chosen from hydrogen,hydrocarbyl, and substituted hydrocarbyl; R⁷ is optionally present, whenpresent it is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n is an integer ≧1.
 35. The polymer of claim 34, whereinR¹, R², R³, R⁴, and R⁵ are hydrogen; n is from 1 to 10; Z is chosen fromsulfur, sulfone, sulfoxide, and selenium; R⁶ is lower chain alkyl, andR⁷, if present, is hydrogen or lower chain alkyl.
 36. The polymer ofclaim 34, wherein the repeat unit comprises Formula (XXa):

wherein: R², R³, R⁴, R⁵, R⁶, R⁸, R⁹, and R¹⁰ are independently chosenfrom hydrogen, hydrocarbyl, and substituted hydrocarbyl; R⁷ and R¹¹ areoptionally present, when present they are independently chosen fromhydrogen, hydrocarbyl, and substituted hydrocarbyl; Y and Z areindependently chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n and m are integers ≧1.
 37. The polymer of claim 36,wherein R², R³, R⁴, R⁵, R⁸ and R⁹ are hydrogen; each of n and m is from1 to 10; Y and Z are independently chosen from sulfur, sulfone,sulfoxide, and selenium; R⁶ and R¹⁰ are lower chain alkyl; and R⁷ andR¹¹, if present, are independently hydrogen or lower chain alkyl. 38.The polymer of claim 34, wherein the repeat unit comprises Formula(XXV):

wherein: p is an integer greater than 1; provided that when p is lessthan 4, then the polymer has a polydispersity index of less than about1.3.
 39. The polymer of claim 34, wherein the polymer is substantiallyfree of a monomer.
 40. The polymer of claim 34, wherein the averagemolecular weight of the polymer is at least about 10,000 Da, at leastabout 100,000 Da, or at least about 1,000,000 Da.
 41. The polymer ofclaim 34, wherein the polymer hydrolyzes in an aqueous solution at a pHbelow about 5.0.
 42. The polymer of claim 34, wherein each repeat unitof the polymer has a configuration chosen from RR, RS, SR, and SS. 43.The polymer of claim 34, wherein the polymer is used as a plasticizer,adhesive, coating, lacquer, film, emulsifier, antioxidant, antimicrobialagent, anticorrosive agent, feed composition, packaging material,consumer product, medical application, or agricultural application. 44.A composition comprising the polymer of claim 34 and a nutritive orpharmaceutical agent.
 45. A composition comprising the polymer of claim34 and at least one additional polymer.
 46. The polymer of claim 34,wherein the polymer comprise a first repeat unit comprising Formula (XX)and at least one second repeat unit.
 47. The polymer of claim 46,wherein the second repeat unit comprises Formula (XX), provided thesecond repeat unit is substituted differently in at least one positionthan the first repeat unit comprising Formula (XX).
 48. The polymer ofclaim 46, wherein the second repeat unit is chosen from a lactide, alactone, a lactam, an hydroxyl alkanoate, an hydroxyl ester, a cyclicether, a tetrahydrofuran, a dioxane, a dioxanone, and mixtures thereof.49. A polymer comprising Formula (XXI)

wherein: R is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; X is chosen from oxygen and nitrogen; and p is an integergreater than
 1. 50. The polymer of claim 49, wherein the polymercomprises Formula (XXVI):

wherein: R is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; X is chosen from oxygen and nitrogen; and p is an integergreater than 1; provided that when p is less than 4, then the polymerhas a polydispersity index of less than about 1.3.
 51. The polymer ofclaim 50, wherein X is oxygen and R is alkyl.
 52. A process for forminga polymer, the process comprising contacting a plurality of compoundscomprising Formula (II):

with a catalyst to form the polymer comprising a repeat unit comprisingFormula (XX):

wherein: R¹, R², R³, R⁴, and R⁵ are independently chosen from hydrogen,hydrocarbyl, and substituted hydrocarbyl; R⁶ is chosen from hydrogen,hydrocarbyl, and substituted hydrocarbyl; R⁷ is optionally present, whenpresent it is chosen from hydrogen, hydrocarbyl, and substitutedhydrocarbyl; Z is chosen from nitrogen, sulfur, sulfone, sulfoxide, andselenium; and n is an integer ≧1.
 53. The process of claim 50, whereinthe compound comprises Formula (V) and the repeat unit comprises Formula(XXV):


54. The process of claim 50, wherein the catalyst is tin(II) octanoateand the process is conducted at a temperature from about 120° C. toabout 180° C. under an inert atmosphere.
 55. The process of claim 50,wherein the process produces a polymer having an average molecularweight of at least about 10,000 Da, at least about 100,000 Da, or atleast about 1,000,000 Da.
 56. The process of claim 50, wherein theprocess further comprises contact with at least one additional monomerto form a copolymer.
 57. The process of claim 54, wherein the additionalmonomer is chosen from a lactide, a lactone, a lactam, ahydroxyalkanoate, a hydroxyester, a cyclic ether, a tetrahydrofuran, adioxane, a dioxanone, and mixtures thereof.